Beta淀粉样肽诱导人成神经瘤母细胞凋亡分子机制的初步探讨
|
摘要
β淀粉样肽(Aβ)是由42个氨基酸组成的肽(Aβ_(1-42)),它是其前体蛋白(APP)剪切后的产物。Aβ以一种不可溶解的沉积物形式积聚在阿尔茨海默病(Alzheimer's disease,AD)患者大脑神经元的周围。增加的Aβ沉积物形式通过诱导神经元的死亡,进而改变AD的病理生理状态包括行为和认知方面的改变。已有报道神经元的细胞凋亡、钙稳态的失调和氧化胁迫与Aβ的神经毒性作用有关。但是有关Aβ神经毒性作用的机制尚未被研究透彻。人成神经瘤母细胞SH-SY5Y细胞是一个较好的神经元模型,它已被广泛用于建立AD模型,本实验利用功能基因组学、蛋白质组学和药理基因组学技术,如高密度基因芯片技术、实时荧光定量PCR技术、二维液相色谱技术、RNAi和免疫印迹技术分析研究Aβ诱导SH-SY5Y细胞凋亡的机制。
1.β-淀粉样肽(1-42)诱导SH-SY5Y细胞发生凋亡的基因表达谱分析
Aβ_(1-42)处理SH-SY5Y细胞。使用CCK-8对细胞活力进行测定。利用Hoechst33342和Annexin-Cy5/Calcein标记的方法,对细胞凋亡进行鉴定。利用安捷伦基因芯片进行表达谱分析。结果显示Aβ_(1-42)以一种浓度依赖性的方式抑制细胞生长,同时能够诱导细胞发生凋亡。芯片分析和实时荧光定量PCR结果显示Aβ_(1-42)处理细胞后,有46个基因的表达水平发生变化,其中包括Caspase-2、Caspase-3、Bax、TP53和TRAF1等基因。
2.β-淀粉样肽(1-42)诱导SH-SY5Y细胞凋亡过程中的蛋白谱表达差异分析
为了进一步从蛋白水平分析Aβ_(1-42)诱导神经元细胞凋亡的机制,本实验利用美国Beckman公司的ProteomeLab~(TM) PF 2D Protein Fractionation System对Aβ_(1-42)处理24小时前后的SH-SY5Y细胞进行蛋白表达差异的分析。结果显示有72个蛋白的表达水平发生变化,并利用MALDI-TOF-MS(matrix assisted laserdesorption/ionization time-of-flight mass spectrometry)鉴定出了三个蛋白包括组蛋白、真核翻译起始因子(eIF-5A)和蛋白质二硫键异构酶(PDIA6)。
3.Caspase-2和TP53在β-淀粉样肽(1-42)诱导神经瘤母细胞凋亡过程中的作用
我们发现在SH-SY5Y细胞中,Aβ_(1-42)能够诱导Caspase-2和TP53的mRNA表达水平的增加,但是有关这两个与细胞凋亡相关的基因在Aβ_(1-42)诱导SH-SY5Y细胞凋亡的作用机制尚需进一步研究。本实验利用转染外源Caspase-2或Caspase-2特异性的siRNA分别过表达Caspase-2或降低Caspase-2的表达;同时利用TP53特异性的抑制剂pifithrin-α和它的siRNA分别降低其蛋白活性和表达水平,从而研究Caspase-2和TP53在Aβ_(1-42)诱导SH-SY5Y细胞凋亡过程中的作用。结果表明,过表达Caspase-2诱导SH-SY5Y细胞凋亡,但并没有增强Aβ_(1-42)诱导的细胞凋亡;而抑制Caspase-2的表达并不能抑制Aβ_(1-42)诱导的神经元性细胞凋亡。同时TP53活性被抑制或表达水平被降低也不能抑制Aβ_(1-42)诱导的神经元性细胞凋亡。Aβ_(1-42)增加Bax/Bcl-xl的比例和Caspase-3的表达,然而,在降低Caspase-2表达水平的时候,同时将TP53的表达水平降低或者抑制其蛋白活性时,Aβ_(1-42)诱导的神经元性细胞凋亡能够被完全抑制。以上结果显示,Caspase-2和TP53是Aβ_(1-42)诱导细胞凋亡过程中的关键调节者。
4.突变重组人胰高血糖素样肽-1抑制β淀粉样肽1-42诱导的细胞凋亡
治疗阿尔茨海默病的选择的靶点之一是阻止β淀粉样肽(Aβ)引发的一系列的生物化学级联反应的发生。已有研究显示胰高血糖素样肽-1(GLP-1)是肠道分泌的一种内生性的促胰岛素释放肽,它能够与脑中的受体结合并具有神经保护效应。利用定点突变和基因重组的技术,我们得到了人突变重组的GLP-1(mGLP-1)。与天然GLP-1受体激动剂相比,这种突变重组的GLP-1呈现出较长的半衰期。本文旨在研究mGLP-1对β淀粉样肽1-42(Aβ_(1-42))细胞毒性的影响并探讨其可能的机制。结果显示:当mGLP-1使用浓度在0.02ng/ml以上时能够促进SH-SY5Y细胞增殖,同时0.1ng/ml mGLP-1和0.5ng/ml的mGLP-1能够降低Aβ_(1-42)诱导的细胞凋亡。同时发现Aβ_(1-42)能够明显引发SH-SY5Y细胞内钙库中的钙离子外流,而mGLP-1有助于维持细胞内钙稳态。Aβ_(1-42)能够显著诱导SH-SY5Y细胞内TP53和Bax的表达,已有报道表明这两个基因参与细胞凋亡过程,而mGLP-1降低Aβ_(1-42)上调TP53和Bax表达的水平。在SH-SY5Y细胞中mGLP-1能够升高细胞质内cAMP浓度,我们鉴定mGLP-1可能通过与细胞中的GLP-1受体相结合从而产生cAMP,最后发挥作用。
5.溶血磷脂酰胆碱对β淀粉样(1-42)肽诱导神经细胞凋亡的影响
许多研究发现脂质平衡态的紊乱在AD发生过程中具有显著的影响作用。同时β淀粉样肽能够引起脂质过氧化反应。但是对于脂质过氧化反应产物和Aβ_(1-42)诱导神经元凋亡之间的关系还有待于研究。本实验的目的是要研究脂质过氧化的一个产物溶血磷脂酰胆碱(lysophosphatidylcholine,LPC)对Aβ_(1-42)诱导SH-SY5Y细胞死亡的影响。实验结果显示长时间用LPC处理SH-SY5Y细胞能够增强Aβ_(1-42)的神经毒性作用。Aβ_(1-42)上调Bax/Bcl-xl的比例,同时增加Caspase-3 mRNA和蛋白水平的表达,Caspase-3的蛋白活性也增加,而TRAF1的mRNA表达水平却被下调。当使用LPC和Aβ_(1-42)同时处理SH-SY5Y细胞时,LPC能够增强Aβ_(1-42)对这些基因表达的影响。已有报道LPC是一个孤儿G蛋白偶联受体G2A的一个特异性配体,所以我们研究LPC对SH-SY5Y细胞内钙离子浓度水平的影响。实验结果显示LPC能够增强Aβ_(1-42)诱导的细胞内钙离子浓度增加的程度。此外,我们发现Aβ_(1-42)能够显著增加SH-SY5Y细胞内G2A的表达,同时当G2A的表达被特异的siRNA抑制时,LPC对Aβ_(1-42)的神经毒性的影响也降低。这些实验结果表明LPC可能通过孤儿G蛋白偶联受体的信号途径影响Aβ_(1-42)诱导的细胞凋亡。
Amyloid protein(Aβ)is a 42 amino acid peptide,derived fromβ-amyloid precursor protein that accumulates as an insoluble deposit around neurons in Alzheimer's disease(AD).Increased deposition of Aβis thought to contribute to the pathophysiology of AD by inducing neuronal cell death,consequences of which include alterations in AD patients's behaviour and cognition.It has been reported that neuronal apoptosis,calcium dysregulation and oxidative stress are implicated in Aβneurotoxicity.However,the mechanisms,factors and genes involved in this neurotoxic effect have not been yet clearly identified.In the present study,functional genomics, proteomics and pharmacogenomics approach such as high-density microarray, fluorescence real-time quantitative PCR(QPCR),two-dimensional liquid chromatography,RNAi and western blotting techniques were applied to analyze the mechanism ofβ-amyloid-induced apoptosis in cultured SH-SY5Y neuroblastoma cells,a well-characterized cell line that has been extensively used as a neuronal model in AD-related research.
1.Gene expression profile in Aβ_(1-42)-treated SH-SY5Y neuroblastoma cells SH-SY5Y cells were treated with Aβ_(1-42)and cell viability was measured by CCK-8 kit.Apoptosis was detected by Hoechst33342 staining and Annexin V-Cy5/Calcein staining.The gene expression profile has been determined using the Agilent GeneChip Human 1A(V2).Aβ_(1-42)inhibited cell growth in dose-dependent manner and induced neuronal apoptosis.The expression of fourty-six genes was altered including Caspase-2,Caspase-3,Bax,TP53 and TRAF1.
2.Proteomic analysis of SH-SY5Y exposed to Aβ_(1-42)
In order to provide a more complete picture of mechanism in Aβ_(1-42)-induced neuronal apoptosis,a proteomic analysis was carried out with Aβ_(1-42)treatment in SH-SY5Y cells.ProteomeLab~(TM)PF 2D Protein Fractionation System was used to compare the levels of proteins in cell lysates from SH-SY5Y cells exposed Aβ_(1-42) (10μM)for 24h to those in control incubation.Seventy-two proteins were differentially expressed.Three proteins had been identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Aβ_(1-42) exposure of SH-SY5Y cells led to increased histone protein and decreased eIF5A and PDIA6.
3.The role of Caspase-2 and TP53 in Aβ_(1-42)-induced neuronal apoptosis In order to investigate the role of Caspase-2 and TP53 in Aβ_(1-42)-induced SH-SY5Y cell apoptosis,exogenous Caspase-2 or siRNA for Caspase-2 was transfected into SH-SY5Y cells respectively to overexpress Caspase-2 or inhibit the expression of endogenous Caspase-2;Pifithrin-a was applied to block its transcription activity and siRNA for TP53 was transfected for reducing the TP53 expression. Overexpression of Caspase-2 caused apoptosis and exhibited no enhanced effect on apoptosis by Aβ_(1-42).Apoptosis-induced by Aβ_(1-42)was not affected by reduction of Caspase-2.Apoptosis-induced by Aβ_(1-42)was also not repressed by pifithrin-αor siRNA for TP53.The ratio of Bax/Bcl-xl and the expression level of Caspase-3 was increased by Aβ_(1-42).However,the effects of Aβ_(1-42)was abolished by pifithrin-αcombined with siRNA-mediated knockdown of Caspase-2,or by siRNA-mediated knockdown of Caspase-2 and TP53,demonstrating that both Caspase-2 and TP53 were required for Aβ_(1-42)-hiduced apoptosis.
4.Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by Aβ_(1-42)
A therapeutic target for AD is to block the cascade reaction induced by Aβ.It has been demonstrated that Glucagon-like peptide-1(GLP-1),which is an endogenous insulinotropic peptide secreted from the gut,binds to its receptor in the brain and possesses neuroprotective effects.Using site-directed mutagenesis and gene recombination techniques,we generated a mutated recombinant human Glucagon-Like Peptide-1(mGLP-1)which has longer half-life as compared with native GLP-1.This present work aims to examine whether mGLP-1 attenuates Aβ_(1-42)-mediated cytotoxicity in SH-SY5Y cells and to explore the possible mechanisms.Our data indicate that≥0.02ng/mL of mGLP-1 facilitated cell proliferation and 0.1ng/ml and 0.5ng/ml of mGLP-1 rescued SH-SY5Y cells from Aβ_(1-42)-induced apoptosis.Moreover,Aβ_(1-42)treatment dramatically stimulated the release of Ca~(2+)from internal calcium stores in SH-SY5Y cells,while mGLP-1 helped to maintain the intracellular Ca~(2+)homeostasis.Aβ_(1-42)also significantly increased the expression level of TP53 and Bax genes which are involved in apoptotic pathways, and mGLP-1 decreasedAβ_(1-42)-induced up-regulation of TP53 and Bax.Since mGLP-1 treatment elevated cytosolic cAMP concentration in SH-SY5Y cells,we postulate that mGLP-1 may exert its influence via binding to GLP-1 receptors in SH-SY5Y cells and stimulating the production of cAMP.These results suggest that mGLP-1 exhibited neuronal protection properties,and could potentially be a novel therapeutic agent for intervention in Alzheimer's disease.
5.Effects of lysophosphatidylcholine onβ-amyloid-induced neuronal apoptosis
Dysfunctional lipid homeostasis has a significant causative impact on the initiation and progression of AD.It has been known thatβ-amyloid can induce lipid peroxidation.However,the relationship between the lipid peroxidation and Aβ_(1-42) induced neuronal apoptosis remains to be elucidated.We have investigated the effects of lysophosphatidylcholine(LPC),a product of lipid peroxidation,on Aβ_(1-42)-induced SH-SY5Y cell apoptosis.Our results showed that long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of Aβ_(1-42).Furthermore,the Bax/Bcl-xl ratio and the expression levels as well as the activity of Caspase-3 were elevated,while the expression level of TRAF1 was reduced after LPC treatment.Since LPC was reported as a specific ligand for an orphan G-protein coupled receptor G2A,we investigated LPC-mediated changes of calcium level in SH-SY5Y cells.Our results demonstrated that LPC could enhance Aβ_(1-42)-induced elevation of intracellular concentration of calcium.Interestingly,Aβ_(1-42)could significantly increase the expression of G2A in SH-SY5Y cells,while the knockdown of G2A using siRNA could reduce the effects of LPC on Aβ_(1-42)-induced neurotoxicity.These results suggested that the effects of LPC on Aβ_(1-42)-induced apoptosis could be through the signal pathways of the orphan G-protein coupled receptor.
1.β-淀粉样肽(1-42)诱导SH-SY5Y细胞发生凋亡的基因表达谱分析
Aβ_(1-42)处理SH-SY5Y细胞。使用CCK-8对细胞活力进行测定。利用Hoechst33342和Annexin-Cy5/Calcein标记的方法,对细胞凋亡进行鉴定。利用安捷伦基因芯片进行表达谱分析。结果显示Aβ_(1-42)以一种浓度依赖性的方式抑制细胞生长,同时能够诱导细胞发生凋亡。芯片分析和实时荧光定量PCR结果显示Aβ_(1-42)处理细胞后,有46个基因的表达水平发生变化,其中包括Caspase-2、Caspase-3、Bax、TP53和TRAF1等基因。
2.β-淀粉样肽(1-42)诱导SH-SY5Y细胞凋亡过程中的蛋白谱表达差异分析
为了进一步从蛋白水平分析Aβ_(1-42)诱导神经元细胞凋亡的机制,本实验利用美国Beckman公司的ProteomeLab~(TM) PF 2D Protein Fractionation System对Aβ_(1-42)处理24小时前后的SH-SY5Y细胞进行蛋白表达差异的分析。结果显示有72个蛋白的表达水平发生变化,并利用MALDI-TOF-MS(matrix assisted laserdesorption/ionization time-of-flight mass spectrometry)鉴定出了三个蛋白包括组蛋白、真核翻译起始因子(eIF-5A)和蛋白质二硫键异构酶(PDIA6)。
3.Caspase-2和TP53在β-淀粉样肽(1-42)诱导神经瘤母细胞凋亡过程中的作用
我们发现在SH-SY5Y细胞中,Aβ_(1-42)能够诱导Caspase-2和TP53的mRNA表达水平的增加,但是有关这两个与细胞凋亡相关的基因在Aβ_(1-42)诱导SH-SY5Y细胞凋亡的作用机制尚需进一步研究。本实验利用转染外源Caspase-2或Caspase-2特异性的siRNA分别过表达Caspase-2或降低Caspase-2的表达;同时利用TP53特异性的抑制剂pifithrin-α和它的siRNA分别降低其蛋白活性和表达水平,从而研究Caspase-2和TP53在Aβ_(1-42)诱导SH-SY5Y细胞凋亡过程中的作用。结果表明,过表达Caspase-2诱导SH-SY5Y细胞凋亡,但并没有增强Aβ_(1-42)诱导的细胞凋亡;而抑制Caspase-2的表达并不能抑制Aβ_(1-42)诱导的神经元性细胞凋亡。同时TP53活性被抑制或表达水平被降低也不能抑制Aβ_(1-42)诱导的神经元性细胞凋亡。Aβ_(1-42)增加Bax/Bcl-xl的比例和Caspase-3的表达,然而,在降低Caspase-2表达水平的时候,同时将TP53的表达水平降低或者抑制其蛋白活性时,Aβ_(1-42)诱导的神经元性细胞凋亡能够被完全抑制。以上结果显示,Caspase-2和TP53是Aβ_(1-42)诱导细胞凋亡过程中的关键调节者。
4.突变重组人胰高血糖素样肽-1抑制β淀粉样肽1-42诱导的细胞凋亡
治疗阿尔茨海默病的选择的靶点之一是阻止β淀粉样肽(Aβ)引发的一系列的生物化学级联反应的发生。已有研究显示胰高血糖素样肽-1(GLP-1)是肠道分泌的一种内生性的促胰岛素释放肽,它能够与脑中的受体结合并具有神经保护效应。利用定点突变和基因重组的技术,我们得到了人突变重组的GLP-1(mGLP-1)。与天然GLP-1受体激动剂相比,这种突变重组的GLP-1呈现出较长的半衰期。本文旨在研究mGLP-1对β淀粉样肽1-42(Aβ_(1-42))细胞毒性的影响并探讨其可能的机制。结果显示:当mGLP-1使用浓度在0.02ng/ml以上时能够促进SH-SY5Y细胞增殖,同时0.1ng/ml mGLP-1和0.5ng/ml的mGLP-1能够降低Aβ_(1-42)诱导的细胞凋亡。同时发现Aβ_(1-42)能够明显引发SH-SY5Y细胞内钙库中的钙离子外流,而mGLP-1有助于维持细胞内钙稳态。Aβ_(1-42)能够显著诱导SH-SY5Y细胞内TP53和Bax的表达,已有报道表明这两个基因参与细胞凋亡过程,而mGLP-1降低Aβ_(1-42)上调TP53和Bax表达的水平。在SH-SY5Y细胞中mGLP-1能够升高细胞质内cAMP浓度,我们鉴定mGLP-1可能通过与细胞中的GLP-1受体相结合从而产生cAMP,最后发挥作用。
5.溶血磷脂酰胆碱对β淀粉样(1-42)肽诱导神经细胞凋亡的影响
许多研究发现脂质平衡态的紊乱在AD发生过程中具有显著的影响作用。同时β淀粉样肽能够引起脂质过氧化反应。但是对于脂质过氧化反应产物和Aβ_(1-42)诱导神经元凋亡之间的关系还有待于研究。本实验的目的是要研究脂质过氧化的一个产物溶血磷脂酰胆碱(lysophosphatidylcholine,LPC)对Aβ_(1-42)诱导SH-SY5Y细胞死亡的影响。实验结果显示长时间用LPC处理SH-SY5Y细胞能够增强Aβ_(1-42)的神经毒性作用。Aβ_(1-42)上调Bax/Bcl-xl的比例,同时增加Caspase-3 mRNA和蛋白水平的表达,Caspase-3的蛋白活性也增加,而TRAF1的mRNA表达水平却被下调。当使用LPC和Aβ_(1-42)同时处理SH-SY5Y细胞时,LPC能够增强Aβ_(1-42)对这些基因表达的影响。已有报道LPC是一个孤儿G蛋白偶联受体G2A的一个特异性配体,所以我们研究LPC对SH-SY5Y细胞内钙离子浓度水平的影响。实验结果显示LPC能够增强Aβ_(1-42)诱导的细胞内钙离子浓度增加的程度。此外,我们发现Aβ_(1-42)能够显著增加SH-SY5Y细胞内G2A的表达,同时当G2A的表达被特异的siRNA抑制时,LPC对Aβ_(1-42)的神经毒性的影响也降低。这些实验结果表明LPC可能通过孤儿G蛋白偶联受体的信号途径影响Aβ_(1-42)诱导的细胞凋亡。
Amyloid protein(Aβ)is a 42 amino acid peptide,derived fromβ-amyloid precursor protein that accumulates as an insoluble deposit around neurons in Alzheimer's disease(AD).Increased deposition of Aβis thought to contribute to the pathophysiology of AD by inducing neuronal cell death,consequences of which include alterations in AD patients's behaviour and cognition.It has been reported that neuronal apoptosis,calcium dysregulation and oxidative stress are implicated in Aβneurotoxicity.However,the mechanisms,factors and genes involved in this neurotoxic effect have not been yet clearly identified.In the present study,functional genomics, proteomics and pharmacogenomics approach such as high-density microarray, fluorescence real-time quantitative PCR(QPCR),two-dimensional liquid chromatography,RNAi and western blotting techniques were applied to analyze the mechanism ofβ-amyloid-induced apoptosis in cultured SH-SY5Y neuroblastoma cells,a well-characterized cell line that has been extensively used as a neuronal model in AD-related research.
1.Gene expression profile in Aβ_(1-42)-treated SH-SY5Y neuroblastoma cells SH-SY5Y cells were treated with Aβ_(1-42)and cell viability was measured by CCK-8 kit.Apoptosis was detected by Hoechst33342 staining and Annexin V-Cy5/Calcein staining.The gene expression profile has been determined using the Agilent GeneChip Human 1A(V2).Aβ_(1-42)inhibited cell growth in dose-dependent manner and induced neuronal apoptosis.The expression of fourty-six genes was altered including Caspase-2,Caspase-3,Bax,TP53 and TRAF1.
2.Proteomic analysis of SH-SY5Y exposed to Aβ_(1-42)
In order to provide a more complete picture of mechanism in Aβ_(1-42)-induced neuronal apoptosis,a proteomic analysis was carried out with Aβ_(1-42)treatment in SH-SY5Y cells.ProteomeLab~(TM)PF 2D Protein Fractionation System was used to compare the levels of proteins in cell lysates from SH-SY5Y cells exposed Aβ_(1-42) (10μM)for 24h to those in control incubation.Seventy-two proteins were differentially expressed.Three proteins had been identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Aβ_(1-42) exposure of SH-SY5Y cells led to increased histone protein and decreased eIF5A and PDIA6.
3.The role of Caspase-2 and TP53 in Aβ_(1-42)-induced neuronal apoptosis In order to investigate the role of Caspase-2 and TP53 in Aβ_(1-42)-induced SH-SY5Y cell apoptosis,exogenous Caspase-2 or siRNA for Caspase-2 was transfected into SH-SY5Y cells respectively to overexpress Caspase-2 or inhibit the expression of endogenous Caspase-2;Pifithrin-a was applied to block its transcription activity and siRNA for TP53 was transfected for reducing the TP53 expression. Overexpression of Caspase-2 caused apoptosis and exhibited no enhanced effect on apoptosis by Aβ_(1-42).Apoptosis-induced by Aβ_(1-42)was not affected by reduction of Caspase-2.Apoptosis-induced by Aβ_(1-42)was also not repressed by pifithrin-αor siRNA for TP53.The ratio of Bax/Bcl-xl and the expression level of Caspase-3 was increased by Aβ_(1-42).However,the effects of Aβ_(1-42)was abolished by pifithrin-αcombined with siRNA-mediated knockdown of Caspase-2,or by siRNA-mediated knockdown of Caspase-2 and TP53,demonstrating that both Caspase-2 and TP53 were required for Aβ_(1-42)-hiduced apoptosis.
4.Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by Aβ_(1-42)
A therapeutic target for AD is to block the cascade reaction induced by Aβ.It has been demonstrated that Glucagon-like peptide-1(GLP-1),which is an endogenous insulinotropic peptide secreted from the gut,binds to its receptor in the brain and possesses neuroprotective effects.Using site-directed mutagenesis and gene recombination techniques,we generated a mutated recombinant human Glucagon-Like Peptide-1(mGLP-1)which has longer half-life as compared with native GLP-1.This present work aims to examine whether mGLP-1 attenuates Aβ_(1-42)-mediated cytotoxicity in SH-SY5Y cells and to explore the possible mechanisms.Our data indicate that≥0.02ng/mL of mGLP-1 facilitated cell proliferation and 0.1ng/ml and 0.5ng/ml of mGLP-1 rescued SH-SY5Y cells from Aβ_(1-42)-induced apoptosis.Moreover,Aβ_(1-42)treatment dramatically stimulated the release of Ca~(2+)from internal calcium stores in SH-SY5Y cells,while mGLP-1 helped to maintain the intracellular Ca~(2+)homeostasis.Aβ_(1-42)also significantly increased the expression level of TP53 and Bax genes which are involved in apoptotic pathways, and mGLP-1 decreasedAβ_(1-42)-induced up-regulation of TP53 and Bax.Since mGLP-1 treatment elevated cytosolic cAMP concentration in SH-SY5Y cells,we postulate that mGLP-1 may exert its influence via binding to GLP-1 receptors in SH-SY5Y cells and stimulating the production of cAMP.These results suggest that mGLP-1 exhibited neuronal protection properties,and could potentially be a novel therapeutic agent for intervention in Alzheimer's disease.
5.Effects of lysophosphatidylcholine onβ-amyloid-induced neuronal apoptosis
Dysfunctional lipid homeostasis has a significant causative impact on the initiation and progression of AD.It has been known thatβ-amyloid can induce lipid peroxidation.However,the relationship between the lipid peroxidation and Aβ_(1-42) induced neuronal apoptosis remains to be elucidated.We have investigated the effects of lysophosphatidylcholine(LPC),a product of lipid peroxidation,on Aβ_(1-42)-induced SH-SY5Y cell apoptosis.Our results showed that long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of Aβ_(1-42).Furthermore,the Bax/Bcl-xl ratio and the expression levels as well as the activity of Caspase-3 were elevated,while the expression level of TRAF1 was reduced after LPC treatment.Since LPC was reported as a specific ligand for an orphan G-protein coupled receptor G2A,we investigated LPC-mediated changes of calcium level in SH-SY5Y cells.Our results demonstrated that LPC could enhance Aβ_(1-42)-induced elevation of intracellular concentration of calcium.Interestingly,Aβ_(1-42)could significantly increase the expression of G2A in SH-SY5Y cells,while the knockdown of G2A using siRNA could reduce the effects of LPC on Aβ_(1-42)-induced neurotoxicity.These results suggested that the effects of LPC on Aβ_(1-42)-induced apoptosis could be through the signal pathways of the orphan G-protein coupled receptor.
引文
1.Hardy J,Selkoe DJ.The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics.Science(New York,N.Y2002;297(5580):353-6.
2.Wirths O,Multhaup G,Bayer TA.A modified beta-amyloid hypothesis:intraneuronal accumulation of the beta-amyloid peptide--the first step of a fatal cascade.Journal of neurochemistry 2004;91(3):513-20.
3.Selkoe DJ.Alzheimer's disease:genes,proteins,and therapy.Physiological reviews 2001;81(2):741-66.
4.Parihar MS,Hemnani T.Alzheimer's disease pathogenesis and therapeutic interventions.J Clin Neurosci 2004;11(5):456-67.
5.Klein WL,Krafft GA,Finch CE.Targeting small Abeta oligomers:the solution to an Alzheimer's disease conundrum? Trends in neurosciences 2001;24(4):219-24.
6.Younkin SG.The role of A beta 42 in Alzheimer's disease.Journal of physiology,Paris 1998;92(3-4):289-92.
7.Biedler JL,Helson L,Spengler BA.Morphology and growth,tumorigenicity,and cytogenetics of human neuroblastoma cells in continuous culture.Cancer Res 1973;33(11):2643-52.
8.Xiao J,Liu CC,Chen PL,Lee WH.RTNT-1,a novel Rad50-interacting protein,participates in radiation-induced G(2)/M checkpoint control.The Journal of biological chemistry 2001;276(9):6105-11.
9.Mateyak MK,Zakian VA.Human PIF helicase is cell cycle regulated and associates with telomerase.Cell cycle(Georgetown,Tex 2006;5(23):2796-804.
10.Park JY,Helm JF,Zheng W,Ly QP,Hodul PJ,Centeno BA et al.Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8(SLC5A8)in human pancreatic cancer.Pancreas 2008;36(4):e32-9.
11.Perez-Torres S,Cortes R,Tolnay M,Probst A,Palacios JM,Mengod G.Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization.Experimental neurology 2003;182(2):322-34.
12.Lee SY,Choi Y.TRAF1 and its biological functions.Advances in experimental medicine and biology 2007;597:25-31.
13.Caffo M,Caruso G,Galatioto S,Meli F,Cacciola F,Germano A et al.Immunohistochemical study of the extracellular matrix proteins laminin,fibronectin and type Ⅳ collagen in secretory meningiomas.J Clin Neurosci 2008;15(7):806-11.
14.Hwang DY,Cho JS,Lee SH,Chae KR,Lim HJ,Min SH et al.Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw.Experimental neurology 2004;186(1);20-32.
15.Ghadersohi A,Odunsi K,Zhang S,Azrak RG,Bundy BN,Manjili MH et al.Prostate-derived Ets transcription factor as a favorable prognostic marker in ovarian cancer patients.International journal of cancer 2008;123(6):1376-84.
16.Wesoly J,Agarwal S,Sigurdsson S,Bussen W,Van Komen S,Qin J et al.Differential contributions of mammalian Rad54 paralogs to recombination,DNA damage repair,and meiosis.Molecular and cellular biology 2006;26(3):976-89.
17.Pina C,May G,Soneji S,Hong D,Enver T.MLLT3 regulates early human erythroid and megakaryocytic cell fate.Cell stem cell 2008;2(3):264-73.
18.Cheng T,Wang Y,Dai W.Transcription factor egr-1 is involved in phorbol 12-myristate 13-acetate-induced megakaryocytic differentiation of K562 cells.The Journal of biological chemistry 1994;269(49):30848-53.
19.Li Y,Wang Y,Zhang C,Yuan W,Wang J,Zhu C et al.ZNF322,a novel human C2H2 Kruppel-like zinc-finger protein,regulates transcriptional activation in MAPK signaling pathways.Biochemical and biophysical research communications 2004;325(4):1383-92.
20.Noble JA,White AM,Lazzeroni LC,Valdes AM,Mirel DB,Reynolds R et al.A polymorphism in the TCF7 gene,C883 A,is associated with type 1 diabetes.Diabe tes 2003;52(6):1579-82.
21.Iwase S,Januma A,Miyamoto K,Shono N,Honda A,Yanagisawa J et al.Characterization of BHC80 in BRAF-HDAC complex,involved in neuron-specific gene repression.Biochemical and biophysical research communications 2004;322(2):601-8.
22.Pascual M,Vicente M,Monferrer L,Artero R.The Muscleblind family of proteins:an emerging class of regulators of developmentally programmed alternative splicing.Differentiation;research in biological diversity 2006;74(2-3):65-80.
23.Li H,Myeroff L,Smiraglia D,Romero MF,Pretlow TP,Kasturi L et al.SLC5 A8,a sodium transporter,is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.Proceedings of the National Academy of Sciences of the United States of America 2003;100(14):8412-7.
24.Murzik U,Hemmerich P,Weidtkamp-Peters S,Ulbricht T,Bussen W, Hentschel J et al.Rad54B targeting to DNA double-strand break repair sites requires complex formation with S100A11.Molecular biology of the cell 2008;19(7):2926-35.
25.Zhu C,Zhao J,Bibikova M,Leverson JD,Bossy-Wetzel E,Fan JB et al.Functional analysis of human microtubule-based motor proteins,the kinesins and dyneins,in mitosis/cytokinesis using RNA interference.Molecular biology of the cell 2005;16(7):3187-99.
26.Tsao ML,Chao CH,Yeh CT.Interaction of hepatitis C virus F protein with prefoldin 2 perturbs tubulin cytoskeleton organization.Biochemical and biophysical research communications 2006;348(1):271-7.
27.Ashall F,Goate AM.Role of the beta-amyloid precursor protein in Alzheimer's disease.Trends Biochem Sci 1994;19(1):42-6.
28.Forlorn G,Bugiani O,Tagliavini F,Salmona M.Apoptosis-mediated neurotoxicity induced by beta-amyloid and PrP fragments.Molecular and chemical neuropathology/sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid 1996;28(1-3):163-71.
29.Allen JW,Eldadah BA,Huang X,Knoblach SM,Faden AI.Multiple caspases are involved in beta-amyloid-induced neuronal apoptosis.J Neurosci Res 2001;65(1):45-53.
30.Bliss TV,Collingridge GL.A synaptic model of memory:long-term potentiation in the hippocampus.Nature 1993;361(6407):31-9.
31.Choi DW.Glutamate neurotoxicity and diseases of the nervous system.Neuron 1988;1(8):623-34.
32.Bi H,Sze CI.N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer's disease.Journal of the neurological sciences 2002;200(1-2):11-8.
33.Lin X,Liu CC,Gao Q,Zhang X,Wu G,Lee WH.RINT-1 serves as a tumor suppressor and maintains Golgi dynamics and centrosome integrity for cell survival.Molecular and cellular biology 2007;27(13):4905-16.
34.Bonkale WL,Cowburn RF,Ohm TG,Bogdanovic N,Fastbom J.A quantitative autoradiographic study of[3H]cAMP binding to cytosolic and particulate protein kinase A in post-mortem brain staged for Alzheimer's disease neurofibrillary changes and amyloid deposits.Brain research 1999;818(2):383-96.
35.Cowburn RF,Fowler CJ,O'Neill C.Neurotransmitters,signal transduction and second-messengers in Alzheimer's disease.Acta neurologica Scandinavica 1996;165:25-32.
36.Dumaz N,Marais R.Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways.Based on the anniversary prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003at the Special FEBS Meeting in Brussels.The FEBS journal 2005;272(14):3491-504.
37.Stork PJ,Schmitt JM.Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation.Trends in cell biology 2002;12(6):258-66.
38.Wajant H,Henkler F,Scheurich P.The TNF-receptor-associated factor family:scaffold molecules for cytokine receptors,kinases and their regulators.Cellular signalling 2001;13(6):389-400.
39.Bradley JR,Pober JS.Tumor necrosis factor receptor-associated factors (TRAFs).Oncogene 2001;20(44):6482-91.
40.Chung JY,Park YC,Ye H,Wu H.All TRAFs are not created equal:common and distinct molecular mechanisms of TRAF-mediated signal transduction.Journal of cell science 2002;115(Pt 4):679-88.
41.Rothe M,Wong SC,Henzel WJ,Goeddel DV.A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.Cell 1994;78(4):681-92.
42.Mosialos G,Birkenbach M,Yalamanchili R,VanArsdale T,Ware C,Kieff E.The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family.Cell 1995;80(3):389-99.
43.Rothe M,Pan MG,Henzel WJ,Ayres TM,Goeddel DV.The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins.Cell 1995;83(7):1243-52.
44.Wang CY,Mayo MW,Korneluk RG,Goeddel DV,Baldwin AS,Jr.NF-kappaB antiapoptosis:induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.Science(New York,N.Y 1998;281(5383):1680-3.
45.Burgeson RE,Chiquet M,Deutzmann R,Ekblom P,Engel J,Kleinman H et al.A new nomenclature for the laminins.Matrix Biol 1994;14(3):209-11.
46.Chen ZL,Strickland S.Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin.Cell 1997;91(7):917-25.
47.Luckenbill-Edds L.Laminin and the mechanism of neuronal outgrowth.Brain Res Brain Res Rev 1997;23(1-2):1-27.
48.Patton BL,Chiu AY,Sanes JR.Synaptic laminin prevents glial entry into the synaptic cleft.Nature 1998;393(6686):698-701.
49.Indyk JA,Chen ZL,Tsirka SE,Strickland S.Laminin chain expression suggests that laminin-10 is a major isoform in the mouse hippocampus and is degraded by the tissue plasminogen activator/plasmin protease cascade during excitotoxic injury.Neuroscience 2003;116(2):359-71.
50.Castillo GM,Lukito W,Peskind E,Raskind M,Kirschner DA,Yee AG et al.Laminin inhibition of beta-amyloid protein (Abeta)fibrillogenesis and identification of an Abeta binding site localized to the globular domain repeats on the laminin a chain.Journal of neuroscience research 2000;62(3):451-62.
51.Morgan C,Inestrosa NC.Interactions of laminin with the amyloid beta peptide.Implications for Alzheimer's disease.Brazilian journal of medical and biological research=Revista brasileira depesquisas medicas e biologicas /Sociedade Brasileira de Biofisica...[et al 2001;34(5):597-601.
52.Monji A,Tashiro K,Yoshida I,Kaname H,Hayashi Y,Matsuda K et al.Laminin inhibits both Abeta40 and Abeta42 fibril formation but does not affect Abeta40 or Abeta42-induced cytotoxicity in PC12 cells.Neuroscience letters 1999;266(2):85-8.
53.Daniel PT.Dissecting the pathways to death.Leukemia 2000;14(12):2035-44.
54.Deveraux QL,Stennicke HR,Salvesen GS,Reed JC.Endogenous inhibitors of caspases.Journal of clinical immunology 1999;19(6):388-98.
55.Troy CM,Rabacchi SA,Friedman WJ,Frappier TF,Brown K,Shelanski ML. Caspase-2 mediates neuronal cell death induced by beta-amyloid.J Neurosci 2000;20(4):1386-92.
56.Vassar R.Caspase-3 cleavage of GGA3 stabilizes BACE:implications for Alzheimer's disease.Neuron 2007;54(5):671-3.
57.Awasthi A,Matsunaga Y,Yamada T.Amyloid-beta causes apoptosis of neuronal cells via caspase cascade,which can be prevented by amyloid-beta-derived short peptides.Experimental neurology 2005;196(2):282-9.
58.Li R,Yang L,Lindholm K,Konishi Y,Yue X,Hampel H et al.Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death.J Neurosci 2004;24(7):1760-71.
59.Tortosa A,Lopez E,Ferrer I.Bcl-2 and Bax protein expression in Alzheimer's disease.Acta neuropathology 1998;95(4):407-12.
60.Schuler M,Green DR.Mechanisms of p53-dependent apoptosis.Biochemical Society transactions 2001;29(Pt 6):684-8.
61.Qin Z,Sun Z,Huang J,Hu Y,Wu Z,Mei B.Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-beta peptide(1-42).Neuroscience letters 2008;444(3):217-21.
62.Wulf GM,Liou YC,Ryo A,Lee SW,Lu KP.Role of Pin1 in the regulation of p53 stability and p21 transactivation,and cell cycle checkpoints in response to DNA damage.The Journal of biological chemistry 2002;277(50):47976-9.
63.Zacchi P,Gostissa M,Uchida T,Salvagno C,Avolio F,Volinia S et al.The prolyl isomerase Pinl reveals a mechanism to control p53 functions after genotoxic insults.Nature 2002;419(6909):853-7.
64.Butterfield DA,Abdul HM,Opii W,Newman SF,Joshi G,Ansari MA et al.Pinl in Alzheimer's disease.Journal of neurochemistry 2006;98(6):1697-706.
65.Anderson L,Seilhamer J.A comparison of selected mRNA and protein abundances in human liver.Electrophoresis 1997;18(3-4):533-7.
66.Abbott A.A post-genomic challenge:learning to read patterns of protein synthesis.Nature 1999;402(6763):715-20.
67.Shin SJ,Lee SE,Boo JH,Kim M,Yoon YD,Kim SI et al.Profiling proteins related to amyloid deposited brain of Tg2576 mice.Proteomics 2004;4(11):3359-68.
68.Sizova D,Charbaut E,Delalande F,Poirier F,High AA,Parker F et al.Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis.Neurobiology of aging 2007;28(3):357-70.
69.Wood DR,Nye JS,Lamb NJ,Fernandez A,Kitzmann M.Intracellular retention of caveolin 1 in presenilin-deficient cells.The Journal of biological chemistry 2005;280(8):6663-8.
70.David DC,Ittner LM,Gehrig P,Nergenau D,Shepherd C,Halliday G et al.Beta-amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes.Proteomics 2006;6(24):6566-77.
71.Tilleman K,Stevens I,Spittaels K,Haute CV,Clerens S,Van Den Bergh G et al.Differential expression of brain proteins in glycogen synthase kinase-3transgenic mice:a proteomics point of view.Proteomics 2002;2(1):94-104.
72.Osorio C,Sullivan PM,He DN,Mace BE,Ervin JF,Strittmatter WJ et al.Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice.Neurobiology of aging 2007;28(12):1853-62.
73.Poon HF,Farr SA,Banks WA,Pierce WM,Klein JB,Morley JE et al.Proteomic identification of less oxidized brain proteins in aged senescence-accelerated mice following administration of antisense oligonucleotide directed at the Abeta region of amyloid precursor protein.Brain research 2005;138(1):8-16.
74.Poon HF,Joshi G,Sultana R,Farr SA,Banks WA,Morley JE et al Antisense directed at the Abeta region of APP decreases brain oxidative markers in aged senescence accelerated mice.Brain research 2004;1018(1):86-96.
75.Boyd-Kimball D,Sultana R,Poon HF,Lynn BC,Casamenti F,Pepeu G et al.Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid beta-peptide(1-42)into rat brain:implications for Alzheimer's disease.Neuroscience 2005;132(2):313-24.
76.Wilson KE,Marouga R,Prime JE,Pashby DP,Orange PR,Crosier S et al.Comparative proteomic analysis using samples obtained with laser microdissection and saturation dye labelling.Proteomics 2005;5(15):3851-8.
77.Boyd-Kimball D,Poon HF,Lynn BC,Cai J,Pierce WM,Jr.,Klein JB et al.Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Abeta(l-42):implications for Alzheimer's disease.Neurobiology of aging 2006;27(9):1239-49.
78.Gevaert K,Vandekerckhove J.Protein identification methods in proteomics.Electrophoresis 2000;21(6):1145-54.
79.Yan F,Subramanian B,Nakeff A,Barder TJ,Parus SJ,Lubman DM.A comparison of drag-treated and untreated HCT-116 human colon adenocarcinoma cells using a 2-D liquid separation mapping method based upon chromatofocusing PI fractionation.Analytical chemistry 2003;75(10):2299-308.
80.Chen EI,Hewel J,Felding-Habermann B,Yates JR,3rd.Large scale protein profiling by combination of protein fractionation and multidimensional protein identification technology(MudPIT).Mol Cell Proteomics 2006;5(1):53-6.
81.Lee HJ,Lee EY,Kwon MS,Paik YK.Biomarker discovery from the plasma proteome using multidimensional fractionation proteomics.Current opinion in chemical biology 2006;10(1):42-9.
82.Linke T,Ross AC,Harrison EH.Proteomic analysis of rat plasma by two-dimensional liquid chromatography and matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Journal of chromatography 2006;1123(2):160-9.
83.Soldi M,Sarto C,Valsecchi C,Magni F,Proserpio V,Ticozzi D et al.Proteome profile of human urine with two-dimensional liquid phase fractionation.Proteomics 2005;5(10):2641-7.
84.Wang Y,Wu R,Cho KR,Shedden KA,Barder TJ,Lubman DM.Classification of cancer cell lines using an automated two-dimensional liquid mapping method with hierarchical clustering techniques.Mol Cell Proteomics 2006;5(1):43-52.
85.Kang X,Frey DD.Chromatofocusing of peptides and proteins using linear pH gradients formed on strong ion-exchange adsorbents.Biotechnology and bioengineering 2004;87(3):376-87.
86.Boyd-Kimball D,Castegna A,Sultana R,Poon HF,Petroze R,Lynn BC et al.Proteomic identification of proteins oxidized by Abeta(1-42)in synaptosomes:implications for Alzheimer's disease.Brain research 2005;1044(2):206-15.
87.Luger K,Mader AW,Richmond RK,Sargent DF,Richmond TJ.Crystal structure of the nucleosome core particle at 2.8 A resolution.Nature 1997;389(6648):251-60.
88.Jenuwein T,Allis CD.Translating the histone code.Science (New York,N.Y 2001;293(5532):1074-80.
89.Strahl BD,Allis CD.The language of covalent histone modifications.Nature 2000;403(6765):41-5.
90.Kouzarides T.Chromatin modifications and their function.Cell 2007;128(4):693-705.
91.Bergink S,Salomons FA,Hoogstraten D,Groothuis TA,de Waard H,Wu J et al.DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A.Genes & development 2006;20(10):1343-52.
92.Potempska A,Ramakrishna N,Wisniewski HM,Miller DL.Interaction between the beta-amyloid peptide precursor and histones.Archives of biochemistry and biophysics 1993;304(2):448-53.
93.Ajiro K.Histone H2B phosphorylation in mammalian apoptotic cells.An association with DNA fragmentation.The Journal of biological chemistry 2000;275(1):439-43.
94.Thompson JE,Hopkins MT,Taylor C,Wang TW.Regulation of senescence by eukaryotic translation initiation factor 5A:implications for plant growth and development.Trends in plant science 2004;9(4):174-9.
95.Tome ME,Fiser SM,Payne CM,Gerner EW.Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5 A (eIF-5A)and induces apoptosis.The Biochemical journal 1997;328(Pt 3):847-54.
96.Kang HA,Hershey JW.Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae.The Journal of biological chemistry 1994;269(6):3934-40.
97.Hayano T,Hirose M,Kikuchi M.Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell.FEBS letters 1995;377(3):505-11.
98.Darby NJ,van Straaten M,Penka E,Vincentelli R,Kemmink J.Identifying and characterizing a second structural domain of protein disulfide isomerase.FEBS letters 1999;448(1):167-72.
99.Mansur K,Iwahashi Y,Kiryu-Seo S,Su Q,Namikawa K,Yodoi J et al.Up-regulation of thioredoxin expression in motor neurons after nerve injury.Brain research 1998;62(1):86-91.
100.Ferrari DM,Soling HD.The protein disulphide-isomerase family:unravelling a string of folds.The Biochemical journal 1999;339(Pt 1):1-10.
101.Klappa P,Hawkins HC,Freedman RB.Interactions between protein disulphide isomerase and peptides.European journal of biochemistry / FEBS 1997;248(1):37-42.
102.Song J,Quan H,Wang C.Dependence of the anti-chaperone activity of protein disulphide isomerase on its chaperone activity.The Biochemical journal 1997; 328(Pt 3):841-6.
103.Zai A,Rudd MA,Scribner AW,Loscalzo J.Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide.The Journal of clinical investigation 1999;103(3):393-9.
104.Su B,Wang X,Nunomura A,Moreira PI,Lee HG,Perry G et al.Oxidative stress signaling in Alzheimer's disease.Current Alzheimer research 2008;5(6):525-32.
105.Ansari MA,Abdul HM,Joshi G,Opii WO,Butterfield DA.Protective effect of quercetin in primary neurons against Abeta(l-42):relevance to Alzheimer's disease.The Journal of nutritional biochemistry 2009;20(4):269-75.
106.Thornberry NA,Lazebnik Y.Caspases:enemies within.Science 1998;281(5381):1312-6.
107.Nicholson DW.Caspase structure,proteolytic substrates,and function during apoptotic cell death.Cell Death Differ 1999;6(11):1028-42.
108.Li H,Bergeron L,Cryns V,Pasternack MS,Zhu H,Shi L et al Activation of caspase-2 in apoptosis.J Biol Chem 1997;272(34):21010-7.
109.Lopez E,Ferrer I.Staurosporine-and H-7-induced cell death in SH-SY5 Y neuroblastoma cells is associated with caspase-2 and caspase-3 activation,but not with activation of the FAS/FAS-L-caspase-8 signaling pathway.Brain Res Mol Brain Res 2000;85(1-2):61-7.
110.Huo J,Luo RH,Metz S A,Li G.Activation of caspase-2 mediates the apoptosis induced by GTP-depletion in insulin-secreting(HIT-T15)cells.Endocrinology 2002;143(5):1695-704.
111.Cascio C,Guarneri R,Russo D,De Leo G,Guarneri M,Piccoli F et al.A caspase-3-dependent pathway is predominantly activated by the excitotoxin pregnenolone sulfate and requires early and late cytochrome c release and cell-specific caspase-2 activation in the retinal cell death.J Neurochem 2002;83(6):1358-71.
112.Caballero-Benitez A,Moran J.Caspase activation pathways induced by staurosporine and low potassium:role of caspase-2.J Neurosci Res 2003;71(3):383-96.
113.Lamkanfi M,Declercq W,Kalai M,Saelens X,Vandenabeele P.Alice in caspase land.A phylogenetic analysis of caspases from worm to man.Cell Death Differ 2002;9(4):358-61.
114.Fuentes-Prior P,Salvesen GS.The protein structures that shape caspase activity,specificity,activation and inhibition.Biochem J2004;384(Pt 2):201-32.
115.Talanian RV,Quinlan C,Trautz S,Hackett MC,Mankovich JA,Banach D et al.Substrate specificities of caspase family proteases.J Biol Chem 1997;272(15):9677-82.
116.Bergeron L,Perez GI,Macdonald G,Shi L,Sun Y,Jurisicova A et al.Defects in regulation of apoptosis in caspase-2-deficient mice.Genes Dev 1998;12(9):1304-14.
117.Duan H,Dixit VM.RAIDD is a new 'death' adaptor molecule.Nature 1997;385(6611):86-9.
118.Paroni G,Henderson C,Schneider C,Brancolini C.Caspase-2-induced apoptosis is dependent on caspase-9,but its processing during UV-or tumor necrosis factor-dependent cell death requires caspase-3.J Biol Chem 2001;276(24):21907-15.
119.Droin N,Bichat F,Rebe C,Wotawa A,Sordet 0,Hammann A et al.Involvement of caspase-2 long isoform in Fas-mediated cell death of human leukemic cells.Blood 2001;97(6):1835-44.
120.Wang L,Miura M,Bergeron L,Zhu H,Yuan J.Ich-1,an Ice/ced-3-related gene,encodes both positive and negative regulators of programmed cell death.Cell 1994;78(5):739-50.
121.Troy CM,Stefanis L,Greene LA,Shelanski ML.Nedd2 is required for apoptosis after trophic factor withdrawal,but not superoxide dismutase(SOD1)downregulation,in sympathetic neurons and PC12 cells.J Neurosci 1997;17(6):1911-8.
122.Haviv R,Lindenboim L,Yuan J,Stein R.Need for caspase-2 in apoptosis of growth-factor-deprived PC12 cells.JNeurosci Res 1998;52(5):491-7.
123.Troy CM,Rabacchi SA,Hohl JB,Angelastro JM,Greene LA,Shelanski ML.Death in the balance:alternative participation of the caspase-2 and-9 pathways in neuronal death induced by nerve growth factor deprivation.J Neurosci 2001;21(14):5007-16.
124.Henshall DC,Skradski SL,Bonislawski DP,Lan JQ,Simon RP.Caspase-2 activation is redundant during seizure-induced neuronal death.J Neurochem 2001;77(3):886-95.
125.Ahmad M,Srinivasula SM,Hegde R,Mukattash R,Fernandes-Alnemri T,Alnemri ES.Identification and characterization of murine caspase-14,a new member of the caspase family.Cancer Res 1998;58(22):5201-5.
126.Hu S,Snipas SJ,Vincenz C,Salvesen G,Dixit VM.Caspase-14 is a novel developmentally regulated protease.J Biol Chem 1998;273(45):29648-53.
127.Humke EW,Ni J,Dixit VM.ERICE,a novel FLICE-activatable caspase.J Biol Chem 1998;273(25):15702-7.
128.Fridman JS,Lowe SW.Control of apoptosis by p53.Oncogene 2003;22(56):9030-40.
129.Bargonetti J,Manfredi JJ.Multiple roles of the tumor suppressor p53.Current opinion in oncology 2002;14(1):86-91.
130.Vogelstein B,Lane D,Levine AJ.Surfing the p53 network.Nature 2000;408(6810):307-10.
131.Stark GR,Taylor WR.Control of the G2/M transition.Molecular biotechnology 2006;32(3):227-48.
132.Yu J,Zhang L.The transcriptional targets of p53 in apoptosis control.Biochemical and biophysical research communications 2005;331(3):851-8.
133.Ho J,Benchimol S.Transcriptional repression mediated by the p53tumour suppressor.Cell death and differentiation 2003;10(4):404-8.
134.Chipuk JE,Green DR.p53's believe it or not:lessons on transcription-independent death.Journal of clinical immunology 2003;23(5):355-61.
135.Murphy ME,Leu JI,George DL.p53 moves to mitochondria:a turn on the path to apoptosis.Cell cycle(Georgetown,Tex 2004;3(7):836-9.
136.de la Monte SM,Sohn YK,Wands JR.Correlates of p53-and Fas (CD95)-mediated apoptosis in Alzheimer's disease.Journal of the neurological sciences 1997;152(1):73-83.
137.Hughes PE,Alexi T,Schreiber SS.A role for the tumour suppressor gene p53 in regulating neuronal apoptosis.Neuroreport 1997;8(15):v-xii.
138.Sakhi S,Bruce A,Sun N,Tocco G,Baudry M,Schreiber SS.Induction of tumor suppressor p53 and DNA fragmentation in organotypic hippocampal cultures following excitotoxin treatment.Experimental neurology 1997;145(1):81-8.
139.Uberti D,Belloni M,Grilli M,Spano P,Memo M.Induction of tumour-suppressor phosphoprotein p53 in the apoptosis of cultured rat cerebellar neurones triggered by excitatory amino acids.The European journal of neuroscience 1998;10(1):246-54.
140.Xiang H,Kinoshita Y,Knudson CM,Korsmeyer SJ,Schwartzkroin PA,Morrison RS.Bax involvement in p53-mediated neuronal cell death.J Neurosci 1998;18(4):1363-73.
141.Cregan SP,MacLaurin JG,Craig CG,Robertson GS,Nicholson DW,Park DS et al.Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons.J Neurosci 1999;19(18):7860-9.
142.Inamura N,Araki T,Enokido Y,Nishio C,Aizawa S,Hatanaka H.Role of p53 in DNA strand break-induced apoptosis in organotypic slice culture from the mouse cerebellum.Journal of neuroscience research 2000;60(4):450-7.
143.Crumrine RC,Thomas AL,Morgan PF.Attenuation of p53 expression protects against focal ischemic damage in transgenic mice.J Cereb Blood Flow Metab 1994;14(6):887-91.
144.Morrison RS,Wenzel HJ,Kinoshita Y,Robbins CA,Donehower LA,Schwartzkroin PA.Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death.J Neurosci 1996;16(4):1337-45.
145.Lin Y,Ma W,Benchimol S.Pidd,a new death-domain-containing protein,is induced by p53 and promotes apoptosis.Nature genetics 2000;26(1):122-7.
146.Tinel A,Tschopp J.The PIDDosome,a protein complex implicated in activation of caspase-2 in response to genotoxic stress.Science (New York,N 72004;304(5672):843-6.
147.Berube C,Boucher LM,Ma W,Wakeham A,Salmena L,Hakem R et al Apoptosis caused by p53-induced protein with death domain (PIDD)depends on the death adapter protein RAIDD.Proceedings of the National Academy of Sciences of the United States of America 2005;102(40):14314-20.
148.Ren J,Shi M,Liu R,Yang QH,Johnson T,Skarnes WC et al.The Birc6 (Bruce)gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development.Proceedings of the National Academy of Sciences of the United States ofAmerica 2005;102(3):565-70.
149.Seth R,Yang C,Kaushal V,Shah SV,Kaushal GP.p53-dependent caspase-2 activation in mitochondrial release of apoptosis-inducing factor and its role in renal tubular epithelial cell injury.The Journal of biological chemistry 2005;280(35):31230-9.
150.Baptiste-Okoh N,Barsotti AM,Prives C.A role for caspase 2 and PIDD in the process of p53-mediated apoptosis.Proceedings of the National Academy of Sciences of the United States of America 2008;105(6):1937-42.
151.Baptiste-Okoh N,Barsotti AM,Prives C.Caspase 2 is both required for p53-mediated apoptosis and downregulated by p53 in a p21-dependent manner.Cell cycle(Georgetown,Tex 2008;7(9):1133-8.
152.Komarov PG,Komarova EA,Kondratov RV,Christov-Tselkov K,Coon JS,Chernov MV et al.A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy.Science(New York,N.Y 1999;285(5434):1733-7.
153.Enari M,Sakahira H,Yokoyama H,Okawa K,Iwamatsu A,Nagata S.A caspase-activated DNase that degrades DNA during apoptosis,and its inhibitor 1CAD.Nature 1998;391(6662):43-50.
154.Keane RW,Srinivasan A,Foster LM,Testa MP,Ord T,Nonner D et al.Activation of CPP32 during apoptosis of neurons and astrocytes.J Neurosci Res 1997;48(2):168-80.
155.Kuida K,Zheng TS,Na S,Kuan C,Yang D,Karasuyama H et al.Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.Nature 1996;384(6607):368-72.
156.Giovanni A,Keramaris E,Morris EJ,Hou ST,O'Hare M,Dyson N et al.E2F1 mediates death of B-amyloid-treated cortical neurons in a manner independent of p53 and dependent on Bax and caspase 3.J Biol Chem 2000;275(16):11553-60.
157.Jordan J,Galindo MF,Miller RJ.Role of calpain-and interleukin-1 beta converting enzyme-like proteases in the beta-amyloid-induced death of rat hippocampal neurons in culture.Journal of neurochemistry 1997;68(4):1612-21.
158.Mattson MP,Partin J,Begley JG.Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites.Brain Res 1998;807(1-2):167-76.
159.Michaelis ML,Ranciat N,Chen Y,Bechtel M,Ragan R,Hepperle M et al.Protection against beta-amyloid toxicity in primary neurons by paclitaxel(Taxol).JNeurochem 1998;70(4):1623-7.
160.Harada J,Sugimoto M.Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons.Brain Res 1999;842(2):311-23.
161.Wang CN,Chi CW,Lin YL,Chen CF,Shiao YJ.The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons.J Biol Chem 2001;276(7):5287-95.
162.Engidawork E,Gulesserian T,Yoo BC,Cairns N,Lubec G.Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease.Biochem Biophys Res Commun 2001;281(1):84-93.
163.Zhivotovsky B,Orrenius S.Caspase-2 function in response to DNA damage.Biochemical and biophysical research communications 2005;331(3):859-67.
164.Droin N,Beauchemin M,Solary E,Bertrand R.Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade.Cancer Res 2000;60(24):7039-47.
165.Ito A,Uehara T,Nomura Y.Isolation of Ich-1S(caspase-2S)-binding protein that partially inhibits caspase activity.FEBS letters 2000;470(3):360-4.
166.LaFerla FM,Hall CK,Ngo L,Jay G.Extracellular deposition of beta-amyloid upon p53-dependent neuronal cell death in transgenic mice.The Journal of clinical investigation 1996;98(7):1626-32.
167.Jiang M,Milner J.Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells.Genes & development 2003;17(7):832-7.
168.Tyagi A,Singh RP,Agarwal C,Agarwal R.Silibinin activates p53-caspase 2 pathway and causes caspase-mediated cleavage of Cipl/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells:evidence for a regulatory loop between p53 and caspase 2.Carcinogenesis 2006;27(11):2269-80.
169.Vakifahmetoglu H,Olsson M,Orrenius S,Zhivotovsky B.Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage.Oncogene 2006;25(41):5683-92.
170.Qian YH,Han H,Hu XD,Shi LL.Protective effect of ginsenoside Rbl on beta-amyloid protein(l-42)-induced neurotoxicity in cortical neurons.Neurological research 2009.
171.Arulmozhi DK,Portha B.GLP-1 based therapy for type 2 diabetes.Eur JPharm Sci 2006;28(1-2):96-108.
172.Perry T,Greig NH.The glucagon-like peptides:a new genre in therapeutic targets for intervention in Alzheimer's disease.J Alzheimers Dis 2002;4(6):487-96.
173.Perry T,Lahiri DK,Sambamurti K,Chen D,Mattson MP,Egan JM et al Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide(Abeta)levels and protects hippocampal neurons from death induced by Abeta and iron.Journal of neuroscience research 2003;72(5):603-12.
174.Green BD,Liu HK,McCluskey JT,Duffy NA,O'Harte FP,McClenaghan NH et al.Function of a long-term,GLP-1-treated,insulin-secreting cell line is improved by preventing DPP Ⅳ-mediated degradation of GLP-1.Diabetes, obesity & metabolism 2005;7(5):563-9.
175.J.Huang ZW,J.Xu,M.F.Jin,Y.L.Wu,J.Li,.Preparation and application of one human glucagon-like peptide-1 analogue.Application Number 2006;200610024355.X.
176.Wheeler MB,Lu M,Dillon JS,Leng XH,Chen C,Boyd AE,3rd.Functional expression of the rat glucagon-like peptide-Ⅰ receptor,evidence for coupling to both adenylyl cyclase and phospholipase-C.Endocrinology 1993;133(1):57-62.
177.van Engeland M,Nieland LJ,Ramaekers FC,Schutte B,Reutelingsperger CP.Annexin V-affinity assay:a review on an apoptosis detection system based on phosphatidylserine exposure.Cytometry 1998;31(1):1-9.
178.LaFerla FM.Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease.Nat Rev Neurosci 2002;3(11):862-72.
179.Chumakov PM.Function of the p53 gene:choice between life and death Biochemistry 2000;65(1):28-40.
180.Antonsson B.Bax and other pro-apoptotic Bcl-2 family "killer-proteins"and their victim the mitochondrion.Cell and tissue research 2001;306(3):347-61.
181.Perry T,Greig NH.The glucagon-like peptides:a double-edged therapeutic sword? Trends in pharmacological sciences 2003;24(7):377-83.
182.Perry T,Lahiri DK,Chen D,Zhou J,Shaw KT,Egan JM et al A novel neurotrophic property of glucagon-like peptide 1:a promoter of nerve growth factor-mediated differentiation in PC12 cells.The Journal of pharmacology and experimental therapeutics 2002;300(3):958-66.
183.John H,Maronde E,Forssmann WG,Meyer M,Adermann K.N-terminal acetylation protects glucagon-like peptide GLP-1-(7-34)-amide from DPP-Ⅳ-mediated degradation retaining cAMP-and insulin-releasing capacity.European journal of medical research 2008;13(2):73-8.
184.Knudsen LB,Pridal L.Glucagon-like peptide-1-(9-36)amide is a major metabolite of glucagon-like peptide-1-(7-36)amide after in vivo administration to dogs,and it acts as an antagonist on the pancreatic receptor.European journal of pharmacology 1996;318(2-3):429-35.
185.Vahl TP,Paty BW,Fuller BD,Prigeon RL,D'Alessio DA.Effects of GLP-1-(7-36)NH2,GLP-1-(7-37),and GLP-1-(9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans.The Journal of clinical endocrinology and metabolism 2003;88(4):1772-9.
186.Mattson MP.Pathways towards and away from Alzheimer's disease.Nature 2004;430(7000):631-9.
187.Ekinci FJ,Linsley MD,Shea TB.Beta-amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation.Brain research 2000;76(2):389-95.
188.Arispe N,Rojas E,Pollard HB.Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes:blockade by tromethamine and aluminum.Proceedings of the National Academy of Sciences of the United States of America 1993;90(2):567-71.
189.Ferreiro E,Oliveira CR,Pereira C.Involvement of endoplasmic reticulum Ca2+release through ryanodine and inositol 1,4,5-triphosphate receptors in the neurotoxic effects induced by the amyloid-beta peptide.Journal of neuroscience research 2004;76(6):872-80.
190.Ferris CD,Cameron AM,Bredt DS,Huganir RL,Snyder SH.Inositol 1,4,5-trisphosphate receptor is phosphorylated by cyclic AMP-dependent protein kinase at serines 1755 and 1589.Biochemical and biophysical research communications 1991;175(1):192-8.
191.Quinton TM,Brown KD,Dean WL.Inositol 1,4,5-trisphosphate-mediated Ca2+release from platelet internal membranes is regulated by differential phosphorylation.Biochemistry 1996;35(21):6865-71.
192.Hooper C,Meimaridou E,Tavassoli M,Melino G,Lovestone S,Killick R.p53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells.Neuroscience letters 2007;418(1):34-7.
193.Kitamura Y,Shimohama S,Kamoshima W,Matsuoka Y,Nomura Y,Taniguchi T.Changes of p53 in the brains of patients with Alzheimer's disease.Biochemical and biophysical research communications 1997;232(2):418-21.
194.Blasko I,Wagner M,Whitaker N,Grubeck-Loebenstein B,Jansen-Durr P.The amyloid beta peptide abeta(25-35)induces apoptosis independent of p53.FEBS letters 2000;470(2):221-5.
195.Chipuk JE,Kuwana T,Bouchier-Hayes L,Drain NM,Newmeyer DD,Schuler M et al.Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis.Science(New York,AT2004;303(5660):1010-4.
196.Schmidt T,Korner K,Karsunky H,Korsmeyer S,Muller R,Moroy T.The activity of the murine Bax promoter is regulated by Spl/3 and E-box binding proteins but not by p53.Cell death and differentiation 1999;6(9):873-82.
197.Nitsch RM,Blusztajn JK,Pittas AG,Slack BE,Growdon JH,Wurtman RJ.Evidence for a membrane defect in Alzheimer disease brain.Proceedings of the National Academy of Sciences of the United States of America 1992;89(5):1671-5.
198.Blusztajn JK,Lopez Gonzalez-Coviella I,Logue M,Growdon JH,Wurtman RJ.Levels of phospholipid catabolic intermediates,glycerophosphocholine and glycerophosphoethanolamine,are elevated in brains of Alzheimer's disease but not of Down's syndrome patients.Brain research 1990;536(1-2):240-4.
199.Klein J.Membrane breakdown in acute and chronic neurodegeneration:focus on choline-containing phospholipids.J Neural Transm 2000;107(8-9):1027-63.
200.Butterfield DA,Castegna A,Lauderback CM,Drake J.Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death.Neurobiology of aging 2002;23(5):655-64.
201.Matsumoto T,Kobayashi T,Kamata K.Role of lysophosphatidylcholine (LPC)in atherosclerosis.Current medicinal chemistry 2007;14(30):3209-20.
202.Hall SM.The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord.Journal of cell science 1972;10(2):535-46.
203.Jean I,Allamargot C,Barthelaix-Pouplard A,Fressinaud C.Axonal lesions and PDGF-enhanced remyelination in the rat corpus callosum after lysolecithin demyelination.Neuroreport 2002;13(5):627-31.
204.Kostrzewa RM,Segura-Aguilar J.Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection.a review.Neurotoxicity research 2003;5(6):375-83.
205.Iqbal K,Alonso Adel C,El-Akkad E,Gong CX,Haque N,Khatoon S et al.Alzheimer neurofibrillary degeneration:therapeutic targets and high-throughput assays.JMol Neurosci 2003;20(3):425-9.
206.Lin P,Ye RD.The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis.The Journal of biological chemistry 2003;278(16):14379-86.
207.Kabarowski JH,Zhu K,Le LQ,Witte ON,Xu Y.Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A.Science (New York,N.Y 2001;293(5530):702-5.
208.Misonou H,Morishima-Kawashima M,Ihara Y.Oxidative stress induces intracellular accumulation of amyloid beta-protein(Abeta)in human neuroblastoma cells.Biochemistry 2000;39(23):6951-9.
209.Paola D,Domenicotti C,Nitti M,Vitali A,Borghi R,Cottalasso D et al.Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betal and betall PKCs in NT2 cells.Biochemical and biophysical research communications 2000;268(2):642-6.
210.Topuridze ML,Kipiani VA,Pavliashvili NS,Kipiani NV,Petriashvili TG.[Molecular mechanisms of apoptosis].Georgian medical news 2007;(150):38-45.
211.Ivins KJ,Thornton PL,Rohn TT,Cotman CW.Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.Neurobiology of disease 1999;6(5):440-9.
212.Nakagawa T,Zhu H,Morishima N,Li E,Xu J,Yankner BA et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.Nature 2000;403(6765):98-103.
213.Tan J,Town T,Placzek A,Kundtz A,Yu H,Mullan M.Bcl-X(L)inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloidl-40 peptide in PC12 cells.Neuroscience letters 1999;272(1):5-8.
214.Mattson MP,Guo Q,Furukawa K,Pedersen WA.Presenilins,the endoplasmic reticulum,and neuronal apoptosis in Alzheimer's disease.J Neurochem 1998;70(1):1-14.
215.Loo DT,Copani A,Pike CJ,Whittemore ER,Walencewicz AJ,Cotman CW.Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proc Natl Acad Sci USA 1993;90(17):7951-5.
216.LaFerla FM,Tinkle BT,Bieberich CJ,Haudenschild CC,Jay G.The Alzheimer's A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice.Nat Genet 1995;9(1):21-30.
217.Paradis E,Douillard H,Koutroumanis M,Goodyer C,LeBlanc A.Amyloid beta peptide of Alzheimer's disease downregulates Bcl-2 and upregulates bax expression in human neurons.J Neurosci 1996;16(23):7533-9.
218.Salim S,Filling C,Martensson E,Oppermann UC.Lack of quinone reductase activity suggests that amyloid-beta peptide/ERAB induced lipid peroxidation is not directly related to production of reactive oxygen species by redoxcycling.Toxicology 2000;144(1-3):163-8.
219.Akama KT,Albanese C,Pestell RG,Van Eldik LJ.Amyloid beta-peptide stimulates nitric oxide production in astrocytes through an NFkappaB-dependent mechanism.Proc Natl Acad Sci USA 1998;95(10):5795-800.
220.Tjernberg LO,Naslund J,Thyberg J,Gandy SE,Terenius L,Nordstedt C.Generation of Alzheimer amyloid beta peptide through nonspecific proteolysis.J Biol Chem 1997;272(3):1870-5.
221.Fu W,Luo H,Parthasarathy S,Mattson MP.Catecholamines potentiate amyloid beta-peptide neurotoxicity:involvement of oxidative stress,mitochondrial dysfunction,and perturbed calcium homeostasis.Neurobiol Dis 1998;5(4):229-43.
222.Ahn YH,Kim YH,Hong SH,Koh JY.Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture.Exp Neurol 1998;154(1):47-56.
223.Kaltschmidt B,Uherek M,Volk B,Baeuerle PA,Kaltschmidt C.Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease.Proc Natl Acad Sci USA 1997;94(6):2642-7.
224.Guo Q,Sopher BL,Furukawa K,Pham DG,Robinson N,Martin GM et al.Alzheimer's presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid beta-peptide:involvement of calcium and oxyradicals.J Neurosci 1997;17(11):4212-22.
225.Keller JN,Guo Q,Holtsberg FW,Bruce-Keller AJ,Mattson MP.Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and enhanced oxyradical production.J Neurosci 1998;18(12):4439-50.
226.Alberici A,Moratto D,Benussi L,Gasparini L,Ghidoni R,Gatta LB et al.Presenilin 1 protein directly interacts with Bcl-2.J Biol Chem 1999;274(43):30764-9.
227.Stennicke HR,Salvesen GS.Caspases:preparation and characterization.Methods 1999;17(4):313-9.
228.Saleh A,Srinivasula SM,Acharya S,Fishel R,Alnemri ES.Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9activation.J Biol Chem 1999;274(25):17941-5.
229.Zou H,Li Y,Liu X,Wang X.An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.J Biol Chem 1999;274(17):11549-56.
230.Benedict MA,Hu Y,Inohara N,Nunez G.Expression and functional analysis of Apaf-1 isoforms.Extra Wd-40 repeat is required for cytochrome c binding and regulated activation of procaspase-9.J Biol Chem 2000;275(12):8461-8.
231.Srinivasula SM,Ahmad M,Fernandes-Alnemri T,Alnemri ES.Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.Mol Cell 1998;1(7):949-57.
232.Kawatani M,Imoto M.Deletion of the BH1 domain of Bcl-2 accelerates apoptosis by acting in a dominant negative fashion.J Biol Chem 2003;278(22):19732-42.
233.Micheau O,Thome M,Schneider P,Holler N,Tschopp J,Nicholson DW et al The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex.J Biol Chem 2002;277(47):45162-71.
234.Stennicke HR,Jurgensmeier JM,Shin H,Deveraux Q,Wolf BB,Yang X et al.Pro-caspase-3 is a major physiologic target of caspase-8.J Biol Chem 1998;273(42):27084-90.
235.Stroh C,Schulze-Osthoff K.Death by a thousand cuts:an ever increasing list of caspase substrates.Cell Death Differ 1998;5(12):997-1000.
236.Raff MC.1.Social controls on cell survival and cell death.Nature 1992;356(6368):397-400.
237.Raff MC,Barres BA,Burne JF,Coles HS,Ishizaki Y,Jacobson MD.2.Programmed cell death and the control of cell survival:lessons from the nervous system.Science (New York,NY1993;262(5134):695-700.
238.Kerr JF,Wyllie AH,Currie AR.3.Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.British journal of cancer 1972;26(4):239-57.
239.Cotman CW,Anderson AJ.4.A potential role for apoptosis in neurodegeneration and Alzheimer's disease.Molecular neurobiology 1995;10(1):19-45.
240.Rohn TT,Head E,Su JH,Anderson AJ,Bahr BA,Cotman CW et al.5.Correlation between caspase activation and neurofibrillary tangle formation in Alzheimer's disease.The American journal of pathology 2001;158(1):189-98.
241.Yang F,Sun X,Beech W,Teter B,Wu S,Sigel J et al.6.Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease.The American journal of pathology 1998;152(2):379-89.
242.Gervais FG,Xu D,Robertson GS,Vaillancourt JP,Zhu Y,Huang J et al.7.Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.Cell 1999;97(3): 395-406.
243.Guo H,Albrecht S,Bourdeau M,Petzke T,Bergeron C,LeBlanc AC.8.Active caspase-6 and caspase-6-cleaved tau in neuropil threads,neuritic plaques,and neurofibrillary tangles of Alzheimer's disease.The American journal of pathology 2004;165(2):523-31..
244.Whitson JS,Selkoe DJ,Cotman CW.9.Amyloid beta protein enhances the survival of hippocampal neurons in vitro.Science(New York,N.Y 1989;243(4897):1488-90.
245.Yankner BA,Dawes LR,Fisher S,Villa-Komaroff L,Oster-Granite ML,Neve RL.lO.Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease.Science(New York,NY 1989;245(4916):417-20.
246.Pike CJ,Walencewicz AJ,Glabe CG,Cotman CW.11.In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity.Brain research 1991;563(1-2):311-4.
247.Pike CJ,Burdick D,Walencewicz AJ,Glabe CG,Cotman CW.12.Neurodegeneration induced by beta-amyloid peptides in vitro:the role of peptide assembly state.J Neurosci 1993;13(4):1676-87.
248.Loo DT,Copani A,Pike CJ,Whittemore ER,Walencewicz AJ,Cotman CW.13.Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proceedings of the National Academy of Sciences of the United States of America 1993;90(17):7951-5.
249.Watt JA,Pike CJ,Walencewicz-Wasserman AJ,Cotman CW.14.Ultrastructural analysis of beta-amyloid-induced apoptosis in cultured hippocampal neurons.Brain research 1994;661(1-2):147-56.
250.Masliah E,Iimoto DS,Saitoh T,Hansen LA,Terry RD.15.Increased immunoreactivity of brain spectrin in Alzheimer disease:a marker for synapse loss? Brain research 1990;531(1-2):36-44.
251.Masliah E,Hansen L,Mallory M,Albright T,Terry RD.16.Abnormal brain spectrin immunoreactivity in sprouting neurons in Alzheimer disease.Neuroscience letters 1991;129(1):1-5.
252.Peterson C,Vanderklish P,Seubert P,Cotman C,Lynch G.17.Increased spectrin proteolysis in fibroblasts from aged and Alzheimer donors.Neuroscience letters 1991;121(1-2):239-43.
253.Bahr BA,Tiriveedhi S,Park GY,Lynch G.18.Induction of calpain-mediated spectrin fragments by pathogenic treatments in long-term hippocampal slices.The Journal of pharmacology and experimental therapeutics 1995;273(2):902-8.
254.Saido TC,Yokota M,Nagao S,Yamaura I,Tani E,Tsuchiya T et al.19.SpatiaI resolution of fodrin proteolysis in postischemic brain.The Journal of biological chemistry 1993;268(33):25239-43.
255.Martin SJ,O'Brien GA,Nishioka WK,McGahon AJ,Mahboubi A,Saido TC et al.20.Proteo lysis of fodrin (non-erythroid spectrin)during apoptosis.The Journal of biological chemistry 1995;270(12):6425-8.
256.Vanags DM,Porn-Ares MI,Coppola S,Burgess DH,Orrenius S.21.Protease involvement in fodrin cleavage and phosphatidylserine exposure in apoptosis.The Journal of biological chemistry 1996;271(49):31075-85.
257.Wang KK,Posmantur R,Nath R,McGinnis K,Whitton M,Talanian RV et al.22.Simultaneous degradation of alphaⅡ-and betaⅡ-spectrin by caspase 3(CPP32)in apoptotic cells.The Journal of biological chemistry 1998;273(35):22490-7.
258.Martin SJ,Finucane DM,Amarante-Mendes GP,O'Brien GA,Green DR.23.Phosphatidylserine.externalization during CD95-induced apoptosis of cells and cytoplasts requires ICE/CED-3 protease activity.The Journal of biological chemistry 1996;271(46):28753-6.
259.Nath R,Raser KJ,Stafford D,Hajimohammadreza I,Posner A,Allen H et al.24.Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1beta-converting-enzyme-like protease(s)in apoptotic cells:contributory roles of both protease families in neuronal apoptosis.The Biochemical journal 1996;319(Pt 3):683-90.
260.Chung CW,Song YH,Kim IK,Yoon WJ,Ryu BR,Jo DG et al.25.Proapoptotic effects of tau cleavage product generated by caspase-3.Neurobiology of disease 2001;8(1):162-72.
261.Rohn TT,Rissman RA,Davis MC,Kim YE,Cotman CW,Head E.26.Caspase-9 activation and caspase cleavage of tau in the Alzheimer's disease brain.Neurobiology of disease 2002;11(2):341-54.
262.Gamblin TC,Chen F,Zambrano A,Abraha A,Lagalwar S,Guillozet AL et al.27.Caspase cleavage of tau:linking amyloid and neurofibrillary tangles in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America 2003;100(17):10032-7.
263.Rissman RA,Poon WW,Blurton-Jones M,Oddo S,Torp R,Vitek MP et al.28.Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology.The Journal of clinical investigation 2004;114(1):121-30.
264.Berry RW,Abraha A,Lagalwar S,LaPointe N,Gamblin TC,Cryns VL et al.29.Inhibition of tau polymerization by its carboxy-terminal caspase cleavage fragment.Biochemistry 2003;42(27):8325-31.
265.Tawa P,Hell K,Giroux A,Grimm E,Han Y,Nicholson DW et al.30.Catalytic activity of caspase-3 is required for its degradation:stabilization of the active complex by synthetic inhibitors.Cell death and differentiation 2004;11(4):439-47.
266.Lassus P,Opitz-Araya X,Lazebnik Y.Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization.Science 2002;297(5585):1352-4.
267.Guo Y,Srinivasula SM,Druilhe A,Fernandes-Alnemri T,Alnemri ES.Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria.J Biol Chem 2002;277(16):13430-7.
268.Baliga BC,Colussi PA,Read SH,Dias MM,Jans DA,Kumar S.Role of prodomain in importin-mediated nuclear localization and activation of caspase-2.J Biol Chem 2003;278(7):4899-905.
269.Bonfoco E,Li E,Kolbinger F,Cooper NR.Characterization of a novel proapoptotic caspase-2-and caspase-9-binding protein.J Biol Chem 2001;276(31):29242-50.
270.Mendelsohn AR,Hamer JD,Wang ZB,Brent R.Cyclin D3 activates Caspase 2,connecting cell proliferation with cell death.Proc Natl Acad Sci USA 2002;99(10):6871-6.
271.O'Reilly LA,Ekert P,Harvey N,Marsden V,Cullen L,Vaux DL et al. Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9.Cell Death Differ 2002;9(8):832-41.
272.Mancini M,Machamer CE,Roy S,Nicholson DW,Thoraberry NA,Casciola-Rosen LA et.al.Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis.J Cell Biol 2000;149(3):603-12.
273.Paroni G,Henderson C,Schneider C,Brancolini C.Caspase-2 can trigger cytochrome C release and apoptosis from the nucleus.J Biol Chem 2002;277(17):15147-61.
274.Cote J,Dupuis S,Wu JY.Polypyrimidine track-binding protein binding downstream of caspase-2 alternative exon 9 represses its inclusion.J Biol Chem 2001;276(11):8535-43.
275.Jin K,Nagayama T,Mao X,Kawaguchi K,Hickey RW,Greenberg DA et al.Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral ischemia.J Neurochem 2002;81(1):25-35.
276.Harrison DC,Davis RP,Bond BC,Campbell CA,James MF,Parsons AA et al.Caspase mRNA expression in a rat model of focal cerebral ischemia.Brain Res Mol Brain Res 2001;89(1-2):133-46.
2.Wirths O,Multhaup G,Bayer TA.A modified beta-amyloid hypothesis:intraneuronal accumulation of the beta-amyloid peptide--the first step of a fatal cascade.Journal of neurochemistry 2004;91(3):513-20.
3.Selkoe DJ.Alzheimer's disease:genes,proteins,and therapy.Physiological reviews 2001;81(2):741-66.
4.Parihar MS,Hemnani T.Alzheimer's disease pathogenesis and therapeutic interventions.J Clin Neurosci 2004;11(5):456-67.
5.Klein WL,Krafft GA,Finch CE.Targeting small Abeta oligomers:the solution to an Alzheimer's disease conundrum? Trends in neurosciences 2001;24(4):219-24.
6.Younkin SG.The role of A beta 42 in Alzheimer's disease.Journal of physiology,Paris 1998;92(3-4):289-92.
7.Biedler JL,Helson L,Spengler BA.Morphology and growth,tumorigenicity,and cytogenetics of human neuroblastoma cells in continuous culture.Cancer Res 1973;33(11):2643-52.
8.Xiao J,Liu CC,Chen PL,Lee WH.RTNT-1,a novel Rad50-interacting protein,participates in radiation-induced G(2)/M checkpoint control.The Journal of biological chemistry 2001;276(9):6105-11.
9.Mateyak MK,Zakian VA.Human PIF helicase is cell cycle regulated and associates with telomerase.Cell cycle(Georgetown,Tex 2006;5(23):2796-804.
10.Park JY,Helm JF,Zheng W,Ly QP,Hodul PJ,Centeno BA et al.Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8(SLC5A8)in human pancreatic cancer.Pancreas 2008;36(4):e32-9.
11.Perez-Torres S,Cortes R,Tolnay M,Probst A,Palacios JM,Mengod G.Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization.Experimental neurology 2003;182(2):322-34.
12.Lee SY,Choi Y.TRAF1 and its biological functions.Advances in experimental medicine and biology 2007;597:25-31.
13.Caffo M,Caruso G,Galatioto S,Meli F,Cacciola F,Germano A et al.Immunohistochemical study of the extracellular matrix proteins laminin,fibronectin and type Ⅳ collagen in secretory meningiomas.J Clin Neurosci 2008;15(7):806-11.
14.Hwang DY,Cho JS,Lee SH,Chae KR,Lim HJ,Min SH et al.Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw.Experimental neurology 2004;186(1);20-32.
15.Ghadersohi A,Odunsi K,Zhang S,Azrak RG,Bundy BN,Manjili MH et al.Prostate-derived Ets transcription factor as a favorable prognostic marker in ovarian cancer patients.International journal of cancer 2008;123(6):1376-84.
16.Wesoly J,Agarwal S,Sigurdsson S,Bussen W,Van Komen S,Qin J et al.Differential contributions of mammalian Rad54 paralogs to recombination,DNA damage repair,and meiosis.Molecular and cellular biology 2006;26(3):976-89.
17.Pina C,May G,Soneji S,Hong D,Enver T.MLLT3 regulates early human erythroid and megakaryocytic cell fate.Cell stem cell 2008;2(3):264-73.
18.Cheng T,Wang Y,Dai W.Transcription factor egr-1 is involved in phorbol 12-myristate 13-acetate-induced megakaryocytic differentiation of K562 cells.The Journal of biological chemistry 1994;269(49):30848-53.
19.Li Y,Wang Y,Zhang C,Yuan W,Wang J,Zhu C et al.ZNF322,a novel human C2H2 Kruppel-like zinc-finger protein,regulates transcriptional activation in MAPK signaling pathways.Biochemical and biophysical research communications 2004;325(4):1383-92.
20.Noble JA,White AM,Lazzeroni LC,Valdes AM,Mirel DB,Reynolds R et al.A polymorphism in the TCF7 gene,C883 A,is associated with type 1 diabetes.Diabe tes 2003;52(6):1579-82.
21.Iwase S,Januma A,Miyamoto K,Shono N,Honda A,Yanagisawa J et al.Characterization of BHC80 in BRAF-HDAC complex,involved in neuron-specific gene repression.Biochemical and biophysical research communications 2004;322(2):601-8.
22.Pascual M,Vicente M,Monferrer L,Artero R.The Muscleblind family of proteins:an emerging class of regulators of developmentally programmed alternative splicing.Differentiation;research in biological diversity 2006;74(2-3):65-80.
23.Li H,Myeroff L,Smiraglia D,Romero MF,Pretlow TP,Kasturi L et al.SLC5 A8,a sodium transporter,is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.Proceedings of the National Academy of Sciences of the United States of America 2003;100(14):8412-7.
24.Murzik U,Hemmerich P,Weidtkamp-Peters S,Ulbricht T,Bussen W, Hentschel J et al.Rad54B targeting to DNA double-strand break repair sites requires complex formation with S100A11.Molecular biology of the cell 2008;19(7):2926-35.
25.Zhu C,Zhao J,Bibikova M,Leverson JD,Bossy-Wetzel E,Fan JB et al.Functional analysis of human microtubule-based motor proteins,the kinesins and dyneins,in mitosis/cytokinesis using RNA interference.Molecular biology of the cell 2005;16(7):3187-99.
26.Tsao ML,Chao CH,Yeh CT.Interaction of hepatitis C virus F protein with prefoldin 2 perturbs tubulin cytoskeleton organization.Biochemical and biophysical research communications 2006;348(1):271-7.
27.Ashall F,Goate AM.Role of the beta-amyloid precursor protein in Alzheimer's disease.Trends Biochem Sci 1994;19(1):42-6.
28.Forlorn G,Bugiani O,Tagliavini F,Salmona M.Apoptosis-mediated neurotoxicity induced by beta-amyloid and PrP fragments.Molecular and chemical neuropathology/sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid 1996;28(1-3):163-71.
29.Allen JW,Eldadah BA,Huang X,Knoblach SM,Faden AI.Multiple caspases are involved in beta-amyloid-induced neuronal apoptosis.J Neurosci Res 2001;65(1):45-53.
30.Bliss TV,Collingridge GL.A synaptic model of memory:long-term potentiation in the hippocampus.Nature 1993;361(6407):31-9.
31.Choi DW.Glutamate neurotoxicity and diseases of the nervous system.Neuron 1988;1(8):623-34.
32.Bi H,Sze CI.N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer's disease.Journal of the neurological sciences 2002;200(1-2):11-8.
33.Lin X,Liu CC,Gao Q,Zhang X,Wu G,Lee WH.RINT-1 serves as a tumor suppressor and maintains Golgi dynamics and centrosome integrity for cell survival.Molecular and cellular biology 2007;27(13):4905-16.
34.Bonkale WL,Cowburn RF,Ohm TG,Bogdanovic N,Fastbom J.A quantitative autoradiographic study of[3H]cAMP binding to cytosolic and particulate protein kinase A in post-mortem brain staged for Alzheimer's disease neurofibrillary changes and amyloid deposits.Brain research 1999;818(2):383-96.
35.Cowburn RF,Fowler CJ,O'Neill C.Neurotransmitters,signal transduction and second-messengers in Alzheimer's disease.Acta neurologica Scandinavica 1996;165:25-32.
36.Dumaz N,Marais R.Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways.Based on the anniversary prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003at the Special FEBS Meeting in Brussels.The FEBS journal 2005;272(14):3491-504.
37.Stork PJ,Schmitt JM.Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation.Trends in cell biology 2002;12(6):258-66.
38.Wajant H,Henkler F,Scheurich P.The TNF-receptor-associated factor family:scaffold molecules for cytokine receptors,kinases and their regulators.Cellular signalling 2001;13(6):389-400.
39.Bradley JR,Pober JS.Tumor necrosis factor receptor-associated factors (TRAFs).Oncogene 2001;20(44):6482-91.
40.Chung JY,Park YC,Ye H,Wu H.All TRAFs are not created equal:common and distinct molecular mechanisms of TRAF-mediated signal transduction.Journal of cell science 2002;115(Pt 4):679-88.
41.Rothe M,Wong SC,Henzel WJ,Goeddel DV.A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.Cell 1994;78(4):681-92.
42.Mosialos G,Birkenbach M,Yalamanchili R,VanArsdale T,Ware C,Kieff E.The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family.Cell 1995;80(3):389-99.
43.Rothe M,Pan MG,Henzel WJ,Ayres TM,Goeddel DV.The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins.Cell 1995;83(7):1243-52.
44.Wang CY,Mayo MW,Korneluk RG,Goeddel DV,Baldwin AS,Jr.NF-kappaB antiapoptosis:induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.Science(New York,N.Y 1998;281(5383):1680-3.
45.Burgeson RE,Chiquet M,Deutzmann R,Ekblom P,Engel J,Kleinman H et al.A new nomenclature for the laminins.Matrix Biol 1994;14(3):209-11.
46.Chen ZL,Strickland S.Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin.Cell 1997;91(7):917-25.
47.Luckenbill-Edds L.Laminin and the mechanism of neuronal outgrowth.Brain Res Brain Res Rev 1997;23(1-2):1-27.
48.Patton BL,Chiu AY,Sanes JR.Synaptic laminin prevents glial entry into the synaptic cleft.Nature 1998;393(6686):698-701.
49.Indyk JA,Chen ZL,Tsirka SE,Strickland S.Laminin chain expression suggests that laminin-10 is a major isoform in the mouse hippocampus and is degraded by the tissue plasminogen activator/plasmin protease cascade during excitotoxic injury.Neuroscience 2003;116(2):359-71.
50.Castillo GM,Lukito W,Peskind E,Raskind M,Kirschner DA,Yee AG et al.Laminin inhibition of beta-amyloid protein (Abeta)fibrillogenesis and identification of an Abeta binding site localized to the globular domain repeats on the laminin a chain.Journal of neuroscience research 2000;62(3):451-62.
51.Morgan C,Inestrosa NC.Interactions of laminin with the amyloid beta peptide.Implications for Alzheimer's disease.Brazilian journal of medical and biological research=Revista brasileira depesquisas medicas e biologicas /Sociedade Brasileira de Biofisica...[et al 2001;34(5):597-601.
52.Monji A,Tashiro K,Yoshida I,Kaname H,Hayashi Y,Matsuda K et al.Laminin inhibits both Abeta40 and Abeta42 fibril formation but does not affect Abeta40 or Abeta42-induced cytotoxicity in PC12 cells.Neuroscience letters 1999;266(2):85-8.
53.Daniel PT.Dissecting the pathways to death.Leukemia 2000;14(12):2035-44.
54.Deveraux QL,Stennicke HR,Salvesen GS,Reed JC.Endogenous inhibitors of caspases.Journal of clinical immunology 1999;19(6):388-98.
55.Troy CM,Rabacchi SA,Friedman WJ,Frappier TF,Brown K,Shelanski ML. Caspase-2 mediates neuronal cell death induced by beta-amyloid.J Neurosci 2000;20(4):1386-92.
56.Vassar R.Caspase-3 cleavage of GGA3 stabilizes BACE:implications for Alzheimer's disease.Neuron 2007;54(5):671-3.
57.Awasthi A,Matsunaga Y,Yamada T.Amyloid-beta causes apoptosis of neuronal cells via caspase cascade,which can be prevented by amyloid-beta-derived short peptides.Experimental neurology 2005;196(2):282-9.
58.Li R,Yang L,Lindholm K,Konishi Y,Yue X,Hampel H et al.Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death.J Neurosci 2004;24(7):1760-71.
59.Tortosa A,Lopez E,Ferrer I.Bcl-2 and Bax protein expression in Alzheimer's disease.Acta neuropathology 1998;95(4):407-12.
60.Schuler M,Green DR.Mechanisms of p53-dependent apoptosis.Biochemical Society transactions 2001;29(Pt 6):684-8.
61.Qin Z,Sun Z,Huang J,Hu Y,Wu Z,Mei B.Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-beta peptide(1-42).Neuroscience letters 2008;444(3):217-21.
62.Wulf GM,Liou YC,Ryo A,Lee SW,Lu KP.Role of Pin1 in the regulation of p53 stability and p21 transactivation,and cell cycle checkpoints in response to DNA damage.The Journal of biological chemistry 2002;277(50):47976-9.
63.Zacchi P,Gostissa M,Uchida T,Salvagno C,Avolio F,Volinia S et al.The prolyl isomerase Pinl reveals a mechanism to control p53 functions after genotoxic insults.Nature 2002;419(6909):853-7.
64.Butterfield DA,Abdul HM,Opii W,Newman SF,Joshi G,Ansari MA et al.Pinl in Alzheimer's disease.Journal of neurochemistry 2006;98(6):1697-706.
65.Anderson L,Seilhamer J.A comparison of selected mRNA and protein abundances in human liver.Electrophoresis 1997;18(3-4):533-7.
66.Abbott A.A post-genomic challenge:learning to read patterns of protein synthesis.Nature 1999;402(6763):715-20.
67.Shin SJ,Lee SE,Boo JH,Kim M,Yoon YD,Kim SI et al.Profiling proteins related to amyloid deposited brain of Tg2576 mice.Proteomics 2004;4(11):3359-68.
68.Sizova D,Charbaut E,Delalande F,Poirier F,High AA,Parker F et al.Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis.Neurobiology of aging 2007;28(3):357-70.
69.Wood DR,Nye JS,Lamb NJ,Fernandez A,Kitzmann M.Intracellular retention of caveolin 1 in presenilin-deficient cells.The Journal of biological chemistry 2005;280(8):6663-8.
70.David DC,Ittner LM,Gehrig P,Nergenau D,Shepherd C,Halliday G et al.Beta-amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes.Proteomics 2006;6(24):6566-77.
71.Tilleman K,Stevens I,Spittaels K,Haute CV,Clerens S,Van Den Bergh G et al.Differential expression of brain proteins in glycogen synthase kinase-3transgenic mice:a proteomics point of view.Proteomics 2002;2(1):94-104.
72.Osorio C,Sullivan PM,He DN,Mace BE,Ervin JF,Strittmatter WJ et al.Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice.Neurobiology of aging 2007;28(12):1853-62.
73.Poon HF,Farr SA,Banks WA,Pierce WM,Klein JB,Morley JE et al.Proteomic identification of less oxidized brain proteins in aged senescence-accelerated mice following administration of antisense oligonucleotide directed at the Abeta region of amyloid precursor protein.Brain research 2005;138(1):8-16.
74.Poon HF,Joshi G,Sultana R,Farr SA,Banks WA,Morley JE et al Antisense directed at the Abeta region of APP decreases brain oxidative markers in aged senescence accelerated mice.Brain research 2004;1018(1):86-96.
75.Boyd-Kimball D,Sultana R,Poon HF,Lynn BC,Casamenti F,Pepeu G et al.Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid beta-peptide(1-42)into rat brain:implications for Alzheimer's disease.Neuroscience 2005;132(2):313-24.
76.Wilson KE,Marouga R,Prime JE,Pashby DP,Orange PR,Crosier S et al.Comparative proteomic analysis using samples obtained with laser microdissection and saturation dye labelling.Proteomics 2005;5(15):3851-8.
77.Boyd-Kimball D,Poon HF,Lynn BC,Cai J,Pierce WM,Jr.,Klein JB et al.Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Abeta(l-42):implications for Alzheimer's disease.Neurobiology of aging 2006;27(9):1239-49.
78.Gevaert K,Vandekerckhove J.Protein identification methods in proteomics.Electrophoresis 2000;21(6):1145-54.
79.Yan F,Subramanian B,Nakeff A,Barder TJ,Parus SJ,Lubman DM.A comparison of drag-treated and untreated HCT-116 human colon adenocarcinoma cells using a 2-D liquid separation mapping method based upon chromatofocusing PI fractionation.Analytical chemistry 2003;75(10):2299-308.
80.Chen EI,Hewel J,Felding-Habermann B,Yates JR,3rd.Large scale protein profiling by combination of protein fractionation and multidimensional protein identification technology(MudPIT).Mol Cell Proteomics 2006;5(1):53-6.
81.Lee HJ,Lee EY,Kwon MS,Paik YK.Biomarker discovery from the plasma proteome using multidimensional fractionation proteomics.Current opinion in chemical biology 2006;10(1):42-9.
82.Linke T,Ross AC,Harrison EH.Proteomic analysis of rat plasma by two-dimensional liquid chromatography and matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Journal of chromatography 2006;1123(2):160-9.
83.Soldi M,Sarto C,Valsecchi C,Magni F,Proserpio V,Ticozzi D et al.Proteome profile of human urine with two-dimensional liquid phase fractionation.Proteomics 2005;5(10):2641-7.
84.Wang Y,Wu R,Cho KR,Shedden KA,Barder TJ,Lubman DM.Classification of cancer cell lines using an automated two-dimensional liquid mapping method with hierarchical clustering techniques.Mol Cell Proteomics 2006;5(1):43-52.
85.Kang X,Frey DD.Chromatofocusing of peptides and proteins using linear pH gradients formed on strong ion-exchange adsorbents.Biotechnology and bioengineering 2004;87(3):376-87.
86.Boyd-Kimball D,Castegna A,Sultana R,Poon HF,Petroze R,Lynn BC et al.Proteomic identification of proteins oxidized by Abeta(1-42)in synaptosomes:implications for Alzheimer's disease.Brain research 2005;1044(2):206-15.
87.Luger K,Mader AW,Richmond RK,Sargent DF,Richmond TJ.Crystal structure of the nucleosome core particle at 2.8 A resolution.Nature 1997;389(6648):251-60.
88.Jenuwein T,Allis CD.Translating the histone code.Science (New York,N.Y 2001;293(5532):1074-80.
89.Strahl BD,Allis CD.The language of covalent histone modifications.Nature 2000;403(6765):41-5.
90.Kouzarides T.Chromatin modifications and their function.Cell 2007;128(4):693-705.
91.Bergink S,Salomons FA,Hoogstraten D,Groothuis TA,de Waard H,Wu J et al.DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A.Genes & development 2006;20(10):1343-52.
92.Potempska A,Ramakrishna N,Wisniewski HM,Miller DL.Interaction between the beta-amyloid peptide precursor and histones.Archives of biochemistry and biophysics 1993;304(2):448-53.
93.Ajiro K.Histone H2B phosphorylation in mammalian apoptotic cells.An association with DNA fragmentation.The Journal of biological chemistry 2000;275(1):439-43.
94.Thompson JE,Hopkins MT,Taylor C,Wang TW.Regulation of senescence by eukaryotic translation initiation factor 5A:implications for plant growth and development.Trends in plant science 2004;9(4):174-9.
95.Tome ME,Fiser SM,Payne CM,Gerner EW.Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5 A (eIF-5A)and induces apoptosis.The Biochemical journal 1997;328(Pt 3):847-54.
96.Kang HA,Hershey JW.Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae.The Journal of biological chemistry 1994;269(6):3934-40.
97.Hayano T,Hirose M,Kikuchi M.Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell.FEBS letters 1995;377(3):505-11.
98.Darby NJ,van Straaten M,Penka E,Vincentelli R,Kemmink J.Identifying and characterizing a second structural domain of protein disulfide isomerase.FEBS letters 1999;448(1):167-72.
99.Mansur K,Iwahashi Y,Kiryu-Seo S,Su Q,Namikawa K,Yodoi J et al.Up-regulation of thioredoxin expression in motor neurons after nerve injury.Brain research 1998;62(1):86-91.
100.Ferrari DM,Soling HD.The protein disulphide-isomerase family:unravelling a string of folds.The Biochemical journal 1999;339(Pt 1):1-10.
101.Klappa P,Hawkins HC,Freedman RB.Interactions between protein disulphide isomerase and peptides.European journal of biochemistry / FEBS 1997;248(1):37-42.
102.Song J,Quan H,Wang C.Dependence of the anti-chaperone activity of protein disulphide isomerase on its chaperone activity.The Biochemical journal 1997; 328(Pt 3):841-6.
103.Zai A,Rudd MA,Scribner AW,Loscalzo J.Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide.The Journal of clinical investigation 1999;103(3):393-9.
104.Su B,Wang X,Nunomura A,Moreira PI,Lee HG,Perry G et al.Oxidative stress signaling in Alzheimer's disease.Current Alzheimer research 2008;5(6):525-32.
105.Ansari MA,Abdul HM,Joshi G,Opii WO,Butterfield DA.Protective effect of quercetin in primary neurons against Abeta(l-42):relevance to Alzheimer's disease.The Journal of nutritional biochemistry 2009;20(4):269-75.
106.Thornberry NA,Lazebnik Y.Caspases:enemies within.Science 1998;281(5381):1312-6.
107.Nicholson DW.Caspase structure,proteolytic substrates,and function during apoptotic cell death.Cell Death Differ 1999;6(11):1028-42.
108.Li H,Bergeron L,Cryns V,Pasternack MS,Zhu H,Shi L et al Activation of caspase-2 in apoptosis.J Biol Chem 1997;272(34):21010-7.
109.Lopez E,Ferrer I.Staurosporine-and H-7-induced cell death in SH-SY5 Y neuroblastoma cells is associated with caspase-2 and caspase-3 activation,but not with activation of the FAS/FAS-L-caspase-8 signaling pathway.Brain Res Mol Brain Res 2000;85(1-2):61-7.
110.Huo J,Luo RH,Metz S A,Li G.Activation of caspase-2 mediates the apoptosis induced by GTP-depletion in insulin-secreting(HIT-T15)cells.Endocrinology 2002;143(5):1695-704.
111.Cascio C,Guarneri R,Russo D,De Leo G,Guarneri M,Piccoli F et al.A caspase-3-dependent pathway is predominantly activated by the excitotoxin pregnenolone sulfate and requires early and late cytochrome c release and cell-specific caspase-2 activation in the retinal cell death.J Neurochem 2002;83(6):1358-71.
112.Caballero-Benitez A,Moran J.Caspase activation pathways induced by staurosporine and low potassium:role of caspase-2.J Neurosci Res 2003;71(3):383-96.
113.Lamkanfi M,Declercq W,Kalai M,Saelens X,Vandenabeele P.Alice in caspase land.A phylogenetic analysis of caspases from worm to man.Cell Death Differ 2002;9(4):358-61.
114.Fuentes-Prior P,Salvesen GS.The protein structures that shape caspase activity,specificity,activation and inhibition.Biochem J2004;384(Pt 2):201-32.
115.Talanian RV,Quinlan C,Trautz S,Hackett MC,Mankovich JA,Banach D et al.Substrate specificities of caspase family proteases.J Biol Chem 1997;272(15):9677-82.
116.Bergeron L,Perez GI,Macdonald G,Shi L,Sun Y,Jurisicova A et al.Defects in regulation of apoptosis in caspase-2-deficient mice.Genes Dev 1998;12(9):1304-14.
117.Duan H,Dixit VM.RAIDD is a new 'death' adaptor molecule.Nature 1997;385(6611):86-9.
118.Paroni G,Henderson C,Schneider C,Brancolini C.Caspase-2-induced apoptosis is dependent on caspase-9,but its processing during UV-or tumor necrosis factor-dependent cell death requires caspase-3.J Biol Chem 2001;276(24):21907-15.
119.Droin N,Bichat F,Rebe C,Wotawa A,Sordet 0,Hammann A et al.Involvement of caspase-2 long isoform in Fas-mediated cell death of human leukemic cells.Blood 2001;97(6):1835-44.
120.Wang L,Miura M,Bergeron L,Zhu H,Yuan J.Ich-1,an Ice/ced-3-related gene,encodes both positive and negative regulators of programmed cell death.Cell 1994;78(5):739-50.
121.Troy CM,Stefanis L,Greene LA,Shelanski ML.Nedd2 is required for apoptosis after trophic factor withdrawal,but not superoxide dismutase(SOD1)downregulation,in sympathetic neurons and PC12 cells.J Neurosci 1997;17(6):1911-8.
122.Haviv R,Lindenboim L,Yuan J,Stein R.Need for caspase-2 in apoptosis of growth-factor-deprived PC12 cells.JNeurosci Res 1998;52(5):491-7.
123.Troy CM,Rabacchi SA,Hohl JB,Angelastro JM,Greene LA,Shelanski ML.Death in the balance:alternative participation of the caspase-2 and-9 pathways in neuronal death induced by nerve growth factor deprivation.J Neurosci 2001;21(14):5007-16.
124.Henshall DC,Skradski SL,Bonislawski DP,Lan JQ,Simon RP.Caspase-2 activation is redundant during seizure-induced neuronal death.J Neurochem 2001;77(3):886-95.
125.Ahmad M,Srinivasula SM,Hegde R,Mukattash R,Fernandes-Alnemri T,Alnemri ES.Identification and characterization of murine caspase-14,a new member of the caspase family.Cancer Res 1998;58(22):5201-5.
126.Hu S,Snipas SJ,Vincenz C,Salvesen G,Dixit VM.Caspase-14 is a novel developmentally regulated protease.J Biol Chem 1998;273(45):29648-53.
127.Humke EW,Ni J,Dixit VM.ERICE,a novel FLICE-activatable caspase.J Biol Chem 1998;273(25):15702-7.
128.Fridman JS,Lowe SW.Control of apoptosis by p53.Oncogene 2003;22(56):9030-40.
129.Bargonetti J,Manfredi JJ.Multiple roles of the tumor suppressor p53.Current opinion in oncology 2002;14(1):86-91.
130.Vogelstein B,Lane D,Levine AJ.Surfing the p53 network.Nature 2000;408(6810):307-10.
131.Stark GR,Taylor WR.Control of the G2/M transition.Molecular biotechnology 2006;32(3):227-48.
132.Yu J,Zhang L.The transcriptional targets of p53 in apoptosis control.Biochemical and biophysical research communications 2005;331(3):851-8.
133.Ho J,Benchimol S.Transcriptional repression mediated by the p53tumour suppressor.Cell death and differentiation 2003;10(4):404-8.
134.Chipuk JE,Green DR.p53's believe it or not:lessons on transcription-independent death.Journal of clinical immunology 2003;23(5):355-61.
135.Murphy ME,Leu JI,George DL.p53 moves to mitochondria:a turn on the path to apoptosis.Cell cycle(Georgetown,Tex 2004;3(7):836-9.
136.de la Monte SM,Sohn YK,Wands JR.Correlates of p53-and Fas (CD95)-mediated apoptosis in Alzheimer's disease.Journal of the neurological sciences 1997;152(1):73-83.
137.Hughes PE,Alexi T,Schreiber SS.A role for the tumour suppressor gene p53 in regulating neuronal apoptosis.Neuroreport 1997;8(15):v-xii.
138.Sakhi S,Bruce A,Sun N,Tocco G,Baudry M,Schreiber SS.Induction of tumor suppressor p53 and DNA fragmentation in organotypic hippocampal cultures following excitotoxin treatment.Experimental neurology 1997;145(1):81-8.
139.Uberti D,Belloni M,Grilli M,Spano P,Memo M.Induction of tumour-suppressor phosphoprotein p53 in the apoptosis of cultured rat cerebellar neurones triggered by excitatory amino acids.The European journal of neuroscience 1998;10(1):246-54.
140.Xiang H,Kinoshita Y,Knudson CM,Korsmeyer SJ,Schwartzkroin PA,Morrison RS.Bax involvement in p53-mediated neuronal cell death.J Neurosci 1998;18(4):1363-73.
141.Cregan SP,MacLaurin JG,Craig CG,Robertson GS,Nicholson DW,Park DS et al.Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons.J Neurosci 1999;19(18):7860-9.
142.Inamura N,Araki T,Enokido Y,Nishio C,Aizawa S,Hatanaka H.Role of p53 in DNA strand break-induced apoptosis in organotypic slice culture from the mouse cerebellum.Journal of neuroscience research 2000;60(4):450-7.
143.Crumrine RC,Thomas AL,Morgan PF.Attenuation of p53 expression protects against focal ischemic damage in transgenic mice.J Cereb Blood Flow Metab 1994;14(6):887-91.
144.Morrison RS,Wenzel HJ,Kinoshita Y,Robbins CA,Donehower LA,Schwartzkroin PA.Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death.J Neurosci 1996;16(4):1337-45.
145.Lin Y,Ma W,Benchimol S.Pidd,a new death-domain-containing protein,is induced by p53 and promotes apoptosis.Nature genetics 2000;26(1):122-7.
146.Tinel A,Tschopp J.The PIDDosome,a protein complex implicated in activation of caspase-2 in response to genotoxic stress.Science (New York,N 72004;304(5672):843-6.
147.Berube C,Boucher LM,Ma W,Wakeham A,Salmena L,Hakem R et al Apoptosis caused by p53-induced protein with death domain (PIDD)depends on the death adapter protein RAIDD.Proceedings of the National Academy of Sciences of the United States of America 2005;102(40):14314-20.
148.Ren J,Shi M,Liu R,Yang QH,Johnson T,Skarnes WC et al.The Birc6 (Bruce)gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development.Proceedings of the National Academy of Sciences of the United States ofAmerica 2005;102(3):565-70.
149.Seth R,Yang C,Kaushal V,Shah SV,Kaushal GP.p53-dependent caspase-2 activation in mitochondrial release of apoptosis-inducing factor and its role in renal tubular epithelial cell injury.The Journal of biological chemistry 2005;280(35):31230-9.
150.Baptiste-Okoh N,Barsotti AM,Prives C.A role for caspase 2 and PIDD in the process of p53-mediated apoptosis.Proceedings of the National Academy of Sciences of the United States of America 2008;105(6):1937-42.
151.Baptiste-Okoh N,Barsotti AM,Prives C.Caspase 2 is both required for p53-mediated apoptosis and downregulated by p53 in a p21-dependent manner.Cell cycle(Georgetown,Tex 2008;7(9):1133-8.
152.Komarov PG,Komarova EA,Kondratov RV,Christov-Tselkov K,Coon JS,Chernov MV et al.A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy.Science(New York,N.Y 1999;285(5434):1733-7.
153.Enari M,Sakahira H,Yokoyama H,Okawa K,Iwamatsu A,Nagata S.A caspase-activated DNase that degrades DNA during apoptosis,and its inhibitor 1CAD.Nature 1998;391(6662):43-50.
154.Keane RW,Srinivasan A,Foster LM,Testa MP,Ord T,Nonner D et al.Activation of CPP32 during apoptosis of neurons and astrocytes.J Neurosci Res 1997;48(2):168-80.
155.Kuida K,Zheng TS,Na S,Kuan C,Yang D,Karasuyama H et al.Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.Nature 1996;384(6607):368-72.
156.Giovanni A,Keramaris E,Morris EJ,Hou ST,O'Hare M,Dyson N et al.E2F1 mediates death of B-amyloid-treated cortical neurons in a manner independent of p53 and dependent on Bax and caspase 3.J Biol Chem 2000;275(16):11553-60.
157.Jordan J,Galindo MF,Miller RJ.Role of calpain-and interleukin-1 beta converting enzyme-like proteases in the beta-amyloid-induced death of rat hippocampal neurons in culture.Journal of neurochemistry 1997;68(4):1612-21.
158.Mattson MP,Partin J,Begley JG.Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites.Brain Res 1998;807(1-2):167-76.
159.Michaelis ML,Ranciat N,Chen Y,Bechtel M,Ragan R,Hepperle M et al.Protection against beta-amyloid toxicity in primary neurons by paclitaxel(Taxol).JNeurochem 1998;70(4):1623-7.
160.Harada J,Sugimoto M.Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons.Brain Res 1999;842(2):311-23.
161.Wang CN,Chi CW,Lin YL,Chen CF,Shiao YJ.The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons.J Biol Chem 2001;276(7):5287-95.
162.Engidawork E,Gulesserian T,Yoo BC,Cairns N,Lubec G.Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease.Biochem Biophys Res Commun 2001;281(1):84-93.
163.Zhivotovsky B,Orrenius S.Caspase-2 function in response to DNA damage.Biochemical and biophysical research communications 2005;331(3):859-67.
164.Droin N,Beauchemin M,Solary E,Bertrand R.Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade.Cancer Res 2000;60(24):7039-47.
165.Ito A,Uehara T,Nomura Y.Isolation of Ich-1S(caspase-2S)-binding protein that partially inhibits caspase activity.FEBS letters 2000;470(3):360-4.
166.LaFerla FM,Hall CK,Ngo L,Jay G.Extracellular deposition of beta-amyloid upon p53-dependent neuronal cell death in transgenic mice.The Journal of clinical investigation 1996;98(7):1626-32.
167.Jiang M,Milner J.Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells.Genes & development 2003;17(7):832-7.
168.Tyagi A,Singh RP,Agarwal C,Agarwal R.Silibinin activates p53-caspase 2 pathway and causes caspase-mediated cleavage of Cipl/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells:evidence for a regulatory loop between p53 and caspase 2.Carcinogenesis 2006;27(11):2269-80.
169.Vakifahmetoglu H,Olsson M,Orrenius S,Zhivotovsky B.Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage.Oncogene 2006;25(41):5683-92.
170.Qian YH,Han H,Hu XD,Shi LL.Protective effect of ginsenoside Rbl on beta-amyloid protein(l-42)-induced neurotoxicity in cortical neurons.Neurological research 2009.
171.Arulmozhi DK,Portha B.GLP-1 based therapy for type 2 diabetes.Eur JPharm Sci 2006;28(1-2):96-108.
172.Perry T,Greig NH.The glucagon-like peptides:a new genre in therapeutic targets for intervention in Alzheimer's disease.J Alzheimers Dis 2002;4(6):487-96.
173.Perry T,Lahiri DK,Sambamurti K,Chen D,Mattson MP,Egan JM et al Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide(Abeta)levels and protects hippocampal neurons from death induced by Abeta and iron.Journal of neuroscience research 2003;72(5):603-12.
174.Green BD,Liu HK,McCluskey JT,Duffy NA,O'Harte FP,McClenaghan NH et al.Function of a long-term,GLP-1-treated,insulin-secreting cell line is improved by preventing DPP Ⅳ-mediated degradation of GLP-1.Diabetes, obesity & metabolism 2005;7(5):563-9.
175.J.Huang ZW,J.Xu,M.F.Jin,Y.L.Wu,J.Li,.Preparation and application of one human glucagon-like peptide-1 analogue.Application Number 2006;200610024355.X.
176.Wheeler MB,Lu M,Dillon JS,Leng XH,Chen C,Boyd AE,3rd.Functional expression of the rat glucagon-like peptide-Ⅰ receptor,evidence for coupling to both adenylyl cyclase and phospholipase-C.Endocrinology 1993;133(1):57-62.
177.van Engeland M,Nieland LJ,Ramaekers FC,Schutte B,Reutelingsperger CP.Annexin V-affinity assay:a review on an apoptosis detection system based on phosphatidylserine exposure.Cytometry 1998;31(1):1-9.
178.LaFerla FM.Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease.Nat Rev Neurosci 2002;3(11):862-72.
179.Chumakov PM.Function of the p53 gene:choice between life and death Biochemistry 2000;65(1):28-40.
180.Antonsson B.Bax and other pro-apoptotic Bcl-2 family "killer-proteins"and their victim the mitochondrion.Cell and tissue research 2001;306(3):347-61.
181.Perry T,Greig NH.The glucagon-like peptides:a double-edged therapeutic sword? Trends in pharmacological sciences 2003;24(7):377-83.
182.Perry T,Lahiri DK,Chen D,Zhou J,Shaw KT,Egan JM et al A novel neurotrophic property of glucagon-like peptide 1:a promoter of nerve growth factor-mediated differentiation in PC12 cells.The Journal of pharmacology and experimental therapeutics 2002;300(3):958-66.
183.John H,Maronde E,Forssmann WG,Meyer M,Adermann K.N-terminal acetylation protects glucagon-like peptide GLP-1-(7-34)-amide from DPP-Ⅳ-mediated degradation retaining cAMP-and insulin-releasing capacity.European journal of medical research 2008;13(2):73-8.
184.Knudsen LB,Pridal L.Glucagon-like peptide-1-(9-36)amide is a major metabolite of glucagon-like peptide-1-(7-36)amide after in vivo administration to dogs,and it acts as an antagonist on the pancreatic receptor.European journal of pharmacology 1996;318(2-3):429-35.
185.Vahl TP,Paty BW,Fuller BD,Prigeon RL,D'Alessio DA.Effects of GLP-1-(7-36)NH2,GLP-1-(7-37),and GLP-1-(9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans.The Journal of clinical endocrinology and metabolism 2003;88(4):1772-9.
186.Mattson MP.Pathways towards and away from Alzheimer's disease.Nature 2004;430(7000):631-9.
187.Ekinci FJ,Linsley MD,Shea TB.Beta-amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation.Brain research 2000;76(2):389-95.
188.Arispe N,Rojas E,Pollard HB.Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes:blockade by tromethamine and aluminum.Proceedings of the National Academy of Sciences of the United States of America 1993;90(2):567-71.
189.Ferreiro E,Oliveira CR,Pereira C.Involvement of endoplasmic reticulum Ca2+release through ryanodine and inositol 1,4,5-triphosphate receptors in the neurotoxic effects induced by the amyloid-beta peptide.Journal of neuroscience research 2004;76(6):872-80.
190.Ferris CD,Cameron AM,Bredt DS,Huganir RL,Snyder SH.Inositol 1,4,5-trisphosphate receptor is phosphorylated by cyclic AMP-dependent protein kinase at serines 1755 and 1589.Biochemical and biophysical research communications 1991;175(1):192-8.
191.Quinton TM,Brown KD,Dean WL.Inositol 1,4,5-trisphosphate-mediated Ca2+release from platelet internal membranes is regulated by differential phosphorylation.Biochemistry 1996;35(21):6865-71.
192.Hooper C,Meimaridou E,Tavassoli M,Melino G,Lovestone S,Killick R.p53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells.Neuroscience letters 2007;418(1):34-7.
193.Kitamura Y,Shimohama S,Kamoshima W,Matsuoka Y,Nomura Y,Taniguchi T.Changes of p53 in the brains of patients with Alzheimer's disease.Biochemical and biophysical research communications 1997;232(2):418-21.
194.Blasko I,Wagner M,Whitaker N,Grubeck-Loebenstein B,Jansen-Durr P.The amyloid beta peptide abeta(25-35)induces apoptosis independent of p53.FEBS letters 2000;470(2):221-5.
195.Chipuk JE,Kuwana T,Bouchier-Hayes L,Drain NM,Newmeyer DD,Schuler M et al.Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis.Science(New York,AT2004;303(5660):1010-4.
196.Schmidt T,Korner K,Karsunky H,Korsmeyer S,Muller R,Moroy T.The activity of the murine Bax promoter is regulated by Spl/3 and E-box binding proteins but not by p53.Cell death and differentiation 1999;6(9):873-82.
197.Nitsch RM,Blusztajn JK,Pittas AG,Slack BE,Growdon JH,Wurtman RJ.Evidence for a membrane defect in Alzheimer disease brain.Proceedings of the National Academy of Sciences of the United States of America 1992;89(5):1671-5.
198.Blusztajn JK,Lopez Gonzalez-Coviella I,Logue M,Growdon JH,Wurtman RJ.Levels of phospholipid catabolic intermediates,glycerophosphocholine and glycerophosphoethanolamine,are elevated in brains of Alzheimer's disease but not of Down's syndrome patients.Brain research 1990;536(1-2):240-4.
199.Klein J.Membrane breakdown in acute and chronic neurodegeneration:focus on choline-containing phospholipids.J Neural Transm 2000;107(8-9):1027-63.
200.Butterfield DA,Castegna A,Lauderback CM,Drake J.Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death.Neurobiology of aging 2002;23(5):655-64.
201.Matsumoto T,Kobayashi T,Kamata K.Role of lysophosphatidylcholine (LPC)in atherosclerosis.Current medicinal chemistry 2007;14(30):3209-20.
202.Hall SM.The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord.Journal of cell science 1972;10(2):535-46.
203.Jean I,Allamargot C,Barthelaix-Pouplard A,Fressinaud C.Axonal lesions and PDGF-enhanced remyelination in the rat corpus callosum after lysolecithin demyelination.Neuroreport 2002;13(5):627-31.
204.Kostrzewa RM,Segura-Aguilar J.Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection.a review.Neurotoxicity research 2003;5(6):375-83.
205.Iqbal K,Alonso Adel C,El-Akkad E,Gong CX,Haque N,Khatoon S et al.Alzheimer neurofibrillary degeneration:therapeutic targets and high-throughput assays.JMol Neurosci 2003;20(3):425-9.
206.Lin P,Ye RD.The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis.The Journal of biological chemistry 2003;278(16):14379-86.
207.Kabarowski JH,Zhu K,Le LQ,Witte ON,Xu Y.Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A.Science (New York,N.Y 2001;293(5530):702-5.
208.Misonou H,Morishima-Kawashima M,Ihara Y.Oxidative stress induces intracellular accumulation of amyloid beta-protein(Abeta)in human neuroblastoma cells.Biochemistry 2000;39(23):6951-9.
209.Paola D,Domenicotti C,Nitti M,Vitali A,Borghi R,Cottalasso D et al.Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betal and betall PKCs in NT2 cells.Biochemical and biophysical research communications 2000;268(2):642-6.
210.Topuridze ML,Kipiani VA,Pavliashvili NS,Kipiani NV,Petriashvili TG.[Molecular mechanisms of apoptosis].Georgian medical news 2007;(150):38-45.
211.Ivins KJ,Thornton PL,Rohn TT,Cotman CW.Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.Neurobiology of disease 1999;6(5):440-9.
212.Nakagawa T,Zhu H,Morishima N,Li E,Xu J,Yankner BA et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.Nature 2000;403(6765):98-103.
213.Tan J,Town T,Placzek A,Kundtz A,Yu H,Mullan M.Bcl-X(L)inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloidl-40 peptide in PC12 cells.Neuroscience letters 1999;272(1):5-8.
214.Mattson MP,Guo Q,Furukawa K,Pedersen WA.Presenilins,the endoplasmic reticulum,and neuronal apoptosis in Alzheimer's disease.J Neurochem 1998;70(1):1-14.
215.Loo DT,Copani A,Pike CJ,Whittemore ER,Walencewicz AJ,Cotman CW.Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proc Natl Acad Sci USA 1993;90(17):7951-5.
216.LaFerla FM,Tinkle BT,Bieberich CJ,Haudenschild CC,Jay G.The Alzheimer's A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice.Nat Genet 1995;9(1):21-30.
217.Paradis E,Douillard H,Koutroumanis M,Goodyer C,LeBlanc A.Amyloid beta peptide of Alzheimer's disease downregulates Bcl-2 and upregulates bax expression in human neurons.J Neurosci 1996;16(23):7533-9.
218.Salim S,Filling C,Martensson E,Oppermann UC.Lack of quinone reductase activity suggests that amyloid-beta peptide/ERAB induced lipid peroxidation is not directly related to production of reactive oxygen species by redoxcycling.Toxicology 2000;144(1-3):163-8.
219.Akama KT,Albanese C,Pestell RG,Van Eldik LJ.Amyloid beta-peptide stimulates nitric oxide production in astrocytes through an NFkappaB-dependent mechanism.Proc Natl Acad Sci USA 1998;95(10):5795-800.
220.Tjernberg LO,Naslund J,Thyberg J,Gandy SE,Terenius L,Nordstedt C.Generation of Alzheimer amyloid beta peptide through nonspecific proteolysis.J Biol Chem 1997;272(3):1870-5.
221.Fu W,Luo H,Parthasarathy S,Mattson MP.Catecholamines potentiate amyloid beta-peptide neurotoxicity:involvement of oxidative stress,mitochondrial dysfunction,and perturbed calcium homeostasis.Neurobiol Dis 1998;5(4):229-43.
222.Ahn YH,Kim YH,Hong SH,Koh JY.Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture.Exp Neurol 1998;154(1):47-56.
223.Kaltschmidt B,Uherek M,Volk B,Baeuerle PA,Kaltschmidt C.Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease.Proc Natl Acad Sci USA 1997;94(6):2642-7.
224.Guo Q,Sopher BL,Furukawa K,Pham DG,Robinson N,Martin GM et al.Alzheimer's presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid beta-peptide:involvement of calcium and oxyradicals.J Neurosci 1997;17(11):4212-22.
225.Keller JN,Guo Q,Holtsberg FW,Bruce-Keller AJ,Mattson MP.Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and enhanced oxyradical production.J Neurosci 1998;18(12):4439-50.
226.Alberici A,Moratto D,Benussi L,Gasparini L,Ghidoni R,Gatta LB et al.Presenilin 1 protein directly interacts with Bcl-2.J Biol Chem 1999;274(43):30764-9.
227.Stennicke HR,Salvesen GS.Caspases:preparation and characterization.Methods 1999;17(4):313-9.
228.Saleh A,Srinivasula SM,Acharya S,Fishel R,Alnemri ES.Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9activation.J Biol Chem 1999;274(25):17941-5.
229.Zou H,Li Y,Liu X,Wang X.An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.J Biol Chem 1999;274(17):11549-56.
230.Benedict MA,Hu Y,Inohara N,Nunez G.Expression and functional analysis of Apaf-1 isoforms.Extra Wd-40 repeat is required for cytochrome c binding and regulated activation of procaspase-9.J Biol Chem 2000;275(12):8461-8.
231.Srinivasula SM,Ahmad M,Fernandes-Alnemri T,Alnemri ES.Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.Mol Cell 1998;1(7):949-57.
232.Kawatani M,Imoto M.Deletion of the BH1 domain of Bcl-2 accelerates apoptosis by acting in a dominant negative fashion.J Biol Chem 2003;278(22):19732-42.
233.Micheau O,Thome M,Schneider P,Holler N,Tschopp J,Nicholson DW et al The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex.J Biol Chem 2002;277(47):45162-71.
234.Stennicke HR,Jurgensmeier JM,Shin H,Deveraux Q,Wolf BB,Yang X et al.Pro-caspase-3 is a major physiologic target of caspase-8.J Biol Chem 1998;273(42):27084-90.
235.Stroh C,Schulze-Osthoff K.Death by a thousand cuts:an ever increasing list of caspase substrates.Cell Death Differ 1998;5(12):997-1000.
236.Raff MC.1.Social controls on cell survival and cell death.Nature 1992;356(6368):397-400.
237.Raff MC,Barres BA,Burne JF,Coles HS,Ishizaki Y,Jacobson MD.2.Programmed cell death and the control of cell survival:lessons from the nervous system.Science (New York,NY1993;262(5134):695-700.
238.Kerr JF,Wyllie AH,Currie AR.3.Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.British journal of cancer 1972;26(4):239-57.
239.Cotman CW,Anderson AJ.4.A potential role for apoptosis in neurodegeneration and Alzheimer's disease.Molecular neurobiology 1995;10(1):19-45.
240.Rohn TT,Head E,Su JH,Anderson AJ,Bahr BA,Cotman CW et al.5.Correlation between caspase activation and neurofibrillary tangle formation in Alzheimer's disease.The American journal of pathology 2001;158(1):189-98.
241.Yang F,Sun X,Beech W,Teter B,Wu S,Sigel J et al.6.Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease.The American journal of pathology 1998;152(2):379-89.
242.Gervais FG,Xu D,Robertson GS,Vaillancourt JP,Zhu Y,Huang J et al.7.Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.Cell 1999;97(3): 395-406.
243.Guo H,Albrecht S,Bourdeau M,Petzke T,Bergeron C,LeBlanc AC.8.Active caspase-6 and caspase-6-cleaved tau in neuropil threads,neuritic plaques,and neurofibrillary tangles of Alzheimer's disease.The American journal of pathology 2004;165(2):523-31..
244.Whitson JS,Selkoe DJ,Cotman CW.9.Amyloid beta protein enhances the survival of hippocampal neurons in vitro.Science(New York,N.Y 1989;243(4897):1488-90.
245.Yankner BA,Dawes LR,Fisher S,Villa-Komaroff L,Oster-Granite ML,Neve RL.lO.Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease.Science(New York,NY 1989;245(4916):417-20.
246.Pike CJ,Walencewicz AJ,Glabe CG,Cotman CW.11.In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity.Brain research 1991;563(1-2):311-4.
247.Pike CJ,Burdick D,Walencewicz AJ,Glabe CG,Cotman CW.12.Neurodegeneration induced by beta-amyloid peptides in vitro:the role of peptide assembly state.J Neurosci 1993;13(4):1676-87.
248.Loo DT,Copani A,Pike CJ,Whittemore ER,Walencewicz AJ,Cotman CW.13.Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proceedings of the National Academy of Sciences of the United States of America 1993;90(17):7951-5.
249.Watt JA,Pike CJ,Walencewicz-Wasserman AJ,Cotman CW.14.Ultrastructural analysis of beta-amyloid-induced apoptosis in cultured hippocampal neurons.Brain research 1994;661(1-2):147-56.
250.Masliah E,Iimoto DS,Saitoh T,Hansen LA,Terry RD.15.Increased immunoreactivity of brain spectrin in Alzheimer disease:a marker for synapse loss? Brain research 1990;531(1-2):36-44.
251.Masliah E,Hansen L,Mallory M,Albright T,Terry RD.16.Abnormal brain spectrin immunoreactivity in sprouting neurons in Alzheimer disease.Neuroscience letters 1991;129(1):1-5.
252.Peterson C,Vanderklish P,Seubert P,Cotman C,Lynch G.17.Increased spectrin proteolysis in fibroblasts from aged and Alzheimer donors.Neuroscience letters 1991;121(1-2):239-43.
253.Bahr BA,Tiriveedhi S,Park GY,Lynch G.18.Induction of calpain-mediated spectrin fragments by pathogenic treatments in long-term hippocampal slices.The Journal of pharmacology and experimental therapeutics 1995;273(2):902-8.
254.Saido TC,Yokota M,Nagao S,Yamaura I,Tani E,Tsuchiya T et al.19.SpatiaI resolution of fodrin proteolysis in postischemic brain.The Journal of biological chemistry 1993;268(33):25239-43.
255.Martin SJ,O'Brien GA,Nishioka WK,McGahon AJ,Mahboubi A,Saido TC et al.20.Proteo lysis of fodrin (non-erythroid spectrin)during apoptosis.The Journal of biological chemistry 1995;270(12):6425-8.
256.Vanags DM,Porn-Ares MI,Coppola S,Burgess DH,Orrenius S.21.Protease involvement in fodrin cleavage and phosphatidylserine exposure in apoptosis.The Journal of biological chemistry 1996;271(49):31075-85.
257.Wang KK,Posmantur R,Nath R,McGinnis K,Whitton M,Talanian RV et al.22.Simultaneous degradation of alphaⅡ-and betaⅡ-spectrin by caspase 3(CPP32)in apoptotic cells.The Journal of biological chemistry 1998;273(35):22490-7.
258.Martin SJ,Finucane DM,Amarante-Mendes GP,O'Brien GA,Green DR.23.Phosphatidylserine.externalization during CD95-induced apoptosis of cells and cytoplasts requires ICE/CED-3 protease activity.The Journal of biological chemistry 1996;271(46):28753-6.
259.Nath R,Raser KJ,Stafford D,Hajimohammadreza I,Posner A,Allen H et al.24.Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1beta-converting-enzyme-like protease(s)in apoptotic cells:contributory roles of both protease families in neuronal apoptosis.The Biochemical journal 1996;319(Pt 3):683-90.
260.Chung CW,Song YH,Kim IK,Yoon WJ,Ryu BR,Jo DG et al.25.Proapoptotic effects of tau cleavage product generated by caspase-3.Neurobiology of disease 2001;8(1):162-72.
261.Rohn TT,Rissman RA,Davis MC,Kim YE,Cotman CW,Head E.26.Caspase-9 activation and caspase cleavage of tau in the Alzheimer's disease brain.Neurobiology of disease 2002;11(2):341-54.
262.Gamblin TC,Chen F,Zambrano A,Abraha A,Lagalwar S,Guillozet AL et al.27.Caspase cleavage of tau:linking amyloid and neurofibrillary tangles in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America 2003;100(17):10032-7.
263.Rissman RA,Poon WW,Blurton-Jones M,Oddo S,Torp R,Vitek MP et al.28.Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology.The Journal of clinical investigation 2004;114(1):121-30.
264.Berry RW,Abraha A,Lagalwar S,LaPointe N,Gamblin TC,Cryns VL et al.29.Inhibition of tau polymerization by its carboxy-terminal caspase cleavage fragment.Biochemistry 2003;42(27):8325-31.
265.Tawa P,Hell K,Giroux A,Grimm E,Han Y,Nicholson DW et al.30.Catalytic activity of caspase-3 is required for its degradation:stabilization of the active complex by synthetic inhibitors.Cell death and differentiation 2004;11(4):439-47.
266.Lassus P,Opitz-Araya X,Lazebnik Y.Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization.Science 2002;297(5585):1352-4.
267.Guo Y,Srinivasula SM,Druilhe A,Fernandes-Alnemri T,Alnemri ES.Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria.J Biol Chem 2002;277(16):13430-7.
268.Baliga BC,Colussi PA,Read SH,Dias MM,Jans DA,Kumar S.Role of prodomain in importin-mediated nuclear localization and activation of caspase-2.J Biol Chem 2003;278(7):4899-905.
269.Bonfoco E,Li E,Kolbinger F,Cooper NR.Characterization of a novel proapoptotic caspase-2-and caspase-9-binding protein.J Biol Chem 2001;276(31):29242-50.
270.Mendelsohn AR,Hamer JD,Wang ZB,Brent R.Cyclin D3 activates Caspase 2,connecting cell proliferation with cell death.Proc Natl Acad Sci USA 2002;99(10):6871-6.
271.O'Reilly LA,Ekert P,Harvey N,Marsden V,Cullen L,Vaux DL et al. Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9.Cell Death Differ 2002;9(8):832-41.
272.Mancini M,Machamer CE,Roy S,Nicholson DW,Thoraberry NA,Casciola-Rosen LA et.al.Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis.J Cell Biol 2000;149(3):603-12.
273.Paroni G,Henderson C,Schneider C,Brancolini C.Caspase-2 can trigger cytochrome C release and apoptosis from the nucleus.J Biol Chem 2002;277(17):15147-61.
274.Cote J,Dupuis S,Wu JY.Polypyrimidine track-binding protein binding downstream of caspase-2 alternative exon 9 represses its inclusion.J Biol Chem 2001;276(11):8535-43.
275.Jin K,Nagayama T,Mao X,Kawaguchi K,Hickey RW,Greenberg DA et al.Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral ischemia.J Neurochem 2002;81(1):25-35.
276.Harrison DC,Davis RP,Bond BC,Campbell CA,James MF,Parsons AA et al.Caspase mRNA expression in a rat model of focal cerebral ischemia.Brain Res Mol Brain Res 2001;89(1-2):133-46.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |