1，5-二咖啡酰奎宁酸预处理对星形胶质细胞脑缺血模型的保护作用及机制的研究
|
摘要
目的观察星形胶质细胞短暂性缺血再灌注损伤过程中胞质和胞核的NF-E2相关因子2(Nrf2)表达变化,分析其核转位情况与细胞氧化损伤水平的相关性。
方法用缺血缺氧4h再灌注24h诱导原代培养的大鼠大脑皮质星形胶质细胞损伤,酶标仪检测各时间点细胞活性氧簇(ROS)和谷胱甘肽(GSH)水平,MTT比色法测定细胞存活率,蛋白免疫印迹分析(Western blot)分别检测星形胶质细胞胞质和胞核内Nrf2表达水平。
结果随着缺血再灌注时间的延长,细胞ROS逐渐增加,GSH含量和存活率逐渐下降(P<0.05),但再灌注12小时与24小时比较,细胞ROS, GSH和存活率无显著性差异(P>0.05)；缺血再灌注早期(再灌注0.5h),胞浆Nrf2表达减少(P<0.05),胞核Nrf2略增高但无统计学差异,而继续再灌注损伤,胞浆和胞核Nrf2均减少,再灌注12小时与24小时比,胞浆和胞核Nrf2表达无显著性差异(P>0.05)。Pearson相关分析显示短暂性缺血再灌注损伤后,胞浆Nrf2表达量与细胞内ROS呈负相关,与GSH含量和细胞存活率呈正相关。
结论Nrf2核转位与短暂性缺血再灌注损伤造成星形胶质细胞氧化应激损伤具有相关性。
目的构建RNA干扰真核表达载体,并对原代培养星形胶质细胞进行转染,验证该方法能否有效抑制细胞Nrf2的表达。
方法选取特异性针对Nrf2基因的寡核苷酸序列,构建重组载体,用绿色荧光蛋白标记并转染原代培养大鼠星形胶质细胞。通过流式细胞术检测绿色荧光来评估转染效率。利用RT-PCR和western blot技术分别检测转染后星形胶质细胞Nrf2 mRNA和蛋白表达水平改变情况以评估RNA干扰效果。
结果构建RNAi真核表达载体并转染星形胶质细胞后,流式细胞术检测提示转染后24h-96h细胞转染率分别为52.19%、59.72%、61.43%、70.61%和62.16%,转染72h瞬时转染效率最高。收获该转染时间点细胞经RT-PCR及western blot显示,siRNA转染可有效抑制星形胶质细胞Nrf2 mRNA和蛋白水平的表达(P<0.05)。
结论成功构建Nrf2 RNA干扰表达载体并转染星形胶质细胞能有效抑制细胞Nrf2基因表达,为进一步研究Nrf2在星形胶质细胞脑缺血损伤模型中的作用提供了重要的实验材料。
目的探讨1,5-二咖啡酰奎宁酸(1,5-dicaffeoylquinic acid,1,5-diCQA)对星形胶质细胞脑缺血模型的保护作用及其可能的机制。
方法用缺糖缺氧再灌注损伤(oxygen and glucose deprivation/reperfusion, OGD/R)处理原代培养星形胶质细胞作为脑缺血的体外模型,实验分为对照组,缺血再灌注组和1,5-diCQA预处理+缺血再灌注组,根据1,5-diCQA预处理的浓度,将后者又分为5,10、20、50、100μmol/L四组。用MTT法测定各组细胞存活率,酶标仪检测细胞ROS含量和GSH水平,western blot检测各组细胞Nrf2蛋白表达水平。为验证1,5-diCQA的保护效应是否依赖于Nrf2核转位,我们又观察了1,5-diCQA预处理对缺血再灌注诱导Nrf2 siRNA组星形胶质细胞损伤的GCL活性、细胞存活率和GSH含量的干预作用。
结果星形胶质细胞经缺血再灌注损伤后,与正常对照组相比,细胞存活率下降,ROS生成增多,GSH耗竭(P<0.05)；不同浓度的1,5-diCQA预处理可以减轻缺血再灌注导致的细胞损伤,且在一定范围内具有量-效关系；50μmol/L的1,5-diCQA预处理可以显著增加缺血再灌注星形胶质细胞的Nrf2核转位和GCL活性；上述保护效应不见于Nrf2 siRNA组星形胶质细胞。
结论1,5-diCQA能改善缺血再灌注诱导的星形胶质细胞氧化应激损伤和细胞死亡,该效应依赖于1,5-diCQA对Nrf2核转位的促进作用。
目的持续性缺糖缺氧(oxygen-glucose deprivation, OGD)处理原代培养星形胶质细胞以模拟脑缺血损伤,观察细胞能量变化及死亡途径并探讨其相关机制。
方法将原代星形胶质细胞分为对照组、OGD组、100μmol/L PD150606预处理+OGD组。分别观察各组星形胶质细胞形态学变化,能量代谢变化,胀亡和凋亡百分比,western blot方法观测各组细胞paxillin、vinculin、vimentin及GFAP四种细胞骨架蛋白表达水平。
结果电镜显示OGD导致细胞出现凋亡和胀亡；OGD使细胞ATP水平呈时间依赖性下降,而凋亡和胀亡细胞比例增高,OGD处理4小时,ATP水平下降低于正常值的35%,此时胀亡成为星形胶质细胞主要死亡途径；持续OGD使星形胶质细胞paxillin、vinculin、vimentin表达逐渐减少,而GFAP先增多后减少,calpain抑制剂PD150606预处理能减少OGD导致的上述蛋白降解,并延迟细胞胀亡。
结论持续性OGD损伤可导致星形胶质细胞凋亡和胀亡；当细胞ATP耗竭到一定阈值(正常值的35%)以下,细胞主要经胀亡途径死亡；calpain调节的细胞骨架蛋白水解参与星形胶质细胞胀亡。
Objective To investigate the expression and the effect of NF-E2-related factor2 on oxidative stress in astrocytes induced by ischemia/reperfusion.
Methods Oxygen-glucose-deprivation and (OGD)/reperfusion to induce the injury of primary cultured rat astrocytes, and ROS level, cellular GSH content, changes of survival rate and the expression of Nrf2 in cytoplasm and nucleus were observed respectively.
Results With the prolongation of OGD/reperfusion, the cellular ROS level was gradually increased, GSH content was delption and the cell viability was decreased. However, at the early stage of injury (reperfusion 0.5h), the expression of Nrf2 was decreased in cytoplasm but increased in nuclear. With the injury continuing, Nrf2 in both cytoplasm and nuclear were decreased. After 12h reperfusion, the expression of Nrf2 showed a tendency toward stabilization.
Conclusion The Nrf2 nuclear translocation possessed correlation with the oxidative stress in astrocytes induced by OGD/reperfusion.
Objective To identify the effect of Nrf2 siRNA transfaction in astrocytes for the silenceof target gene.
Methods The small interfering RNA specific targeted to Nrf2 gene was constructed by chemical synthesis and was transfected into primary culture astrocytes using lipofectamine2000. Transfection efficiency was detected using fluorescence microscopy ans flow cytometry. The expression of Nrf2 mRNA and protein in the tansfected astrocytes was identified by RT-PCR and western blot analysis respectively.
Results The eukaryotic expression vector of Nrf2 was constructed and tansfected primary culture astrocytes. The transfection efficiency was 52.19%、59.72%、61.43%、 70.61% and 62.16% respectively in 24,48,72 and 96h. RT-PCR and western blot analysis showed that Nrf2 siRNA can efficiently suppress Nrf2 mRNA and protein expression (P＜0.05).
Conclusions Transfect Nrf2 siRNA into astrocytes can effectively inhibite Nrf2 mRNA and protein expression, prepare a condition for subsequent research of medical intervention in ischemia model of astrocytes.
Objective To investigate the protective effects of 1,5-diCQA preconditioning on the injury of astrocytes induced by OGD/reperfusion and the related mechanisms.
Methods Oxygen-glucose-deprivation and (OGD)/reperfusion to induce the injury of primary cultured rat astrocytes. The cells were divided into:the control group, OGD/reperfusion group,1,5-diCQA+OGD/reperfusion group. The release of LDH, ROS level, cellular GSH content, changes of survival rate and the expression of Nrf2 in cytoplasm and nucleus, glutamate-cysteine ligase (GCL) activity were observed respectively. The indicators mentioned above were also detected in Nrf2 siRNA tansfected astrocytes to verificated whether the protective effects of 1,5-diCQA depend on the activation of Nrf2/ARE pathway.
Results 1,5-diCQA pretreatment significantly suppressed cell death, reduced the production of reactive oxygen species, prevented glutathione (GSH) depletion, increased the activity of glutamate-cysteine ligase (GCL) and triggered Nrf2 nuclear translocation in astrocytes induced by 4 h OGD and 24 h reperfusion. Interestingly, these protective effects were greatly attenuated in Nrf2 siRNA-transfected cells.
Conclusions 1,5-diCQA has antioxidant signaling properties that upregulate GSH synthesis by stimulating the Nrf2 pathway in astrocytes and protects them from cell death in an in vitro model of ischemia/reperfusion.
Objective To study the effect of persistent oxygen-glucose-deprivation (OGD) on the death pathway of primary culture rat astrocytes and the relevant mechanisms.
Methods The primary culture rat astrocytes were divided into three groups:①the control group:cells maintained in high glucose DMEM supplemented with 20% fetal calf serum;②the cells treated with OGD;③pretreatment with PD 150606 (100μmol/L) before OGD. the changes of the cellular morphology, the energy metabolism of astrocytes, and the percentages of apoptosis or oncosis of the astrocytes induced by OGD were observed respectively, and Western blot was adoped to assay the protein expression of several cytoskeletal proteins, including paxillin, vinculin, vimentin and GFAP.
Results Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and oncosis in individual cells. The cellular ATP content was gradually decreased (P＜0.05) and the percentages of apoptotic and oncotic cells were increased over the OGD time(P＜0.05). After 4 h OGD, the ATP depletion below 35% of control and oncosis became the main pathway of astrocytes death. OGD led to a significant decrease in paxillin, vinculin, vimentin protein levels in a time-dependent manner (P<0.05) while GFAP appeared markedly more than the control at 0.5 h OGD treatment (P＜0.05), then decreased later. Pre-treatment with 100μmol/L Calpain inhibitor PD150606 led to decrease in the loss of cytoskeleton-associated proteins, and delayed the LDH release of astrocytes associated OGD damage.
Conclusion Astrocytes induced by persistent OGD would be go though apoptosis and oncosis, and there was a narrow range of ATP threshold (<35%of the control) that determines astrocytes oncotic death induced by persistent OGD; calpain-mediated hydrolysis of the cytoskeleton-associated proteins may contribute to astrocytes oncosis.
方法用缺血缺氧4h再灌注24h诱导原代培养的大鼠大脑皮质星形胶质细胞损伤,酶标仪检测各时间点细胞活性氧簇(ROS)和谷胱甘肽(GSH)水平,MTT比色法测定细胞存活率,蛋白免疫印迹分析(Western blot)分别检测星形胶质细胞胞质和胞核内Nrf2表达水平。
结果随着缺血再灌注时间的延长,细胞ROS逐渐增加,GSH含量和存活率逐渐下降(P<0.05),但再灌注12小时与24小时比较,细胞ROS, GSH和存活率无显著性差异(P>0.05)；缺血再灌注早期(再灌注0.5h),胞浆Nrf2表达减少(P<0.05),胞核Nrf2略增高但无统计学差异,而继续再灌注损伤,胞浆和胞核Nrf2均减少,再灌注12小时与24小时比,胞浆和胞核Nrf2表达无显著性差异(P>0.05)。Pearson相关分析显示短暂性缺血再灌注损伤后,胞浆Nrf2表达量与细胞内ROS呈负相关,与GSH含量和细胞存活率呈正相关。
结论Nrf2核转位与短暂性缺血再灌注损伤造成星形胶质细胞氧化应激损伤具有相关性。
目的构建RNA干扰真核表达载体,并对原代培养星形胶质细胞进行转染,验证该方法能否有效抑制细胞Nrf2的表达。
方法选取特异性针对Nrf2基因的寡核苷酸序列,构建重组载体,用绿色荧光蛋白标记并转染原代培养大鼠星形胶质细胞。通过流式细胞术检测绿色荧光来评估转染效率。利用RT-PCR和western blot技术分别检测转染后星形胶质细胞Nrf2 mRNA和蛋白表达水平改变情况以评估RNA干扰效果。
结果构建RNAi真核表达载体并转染星形胶质细胞后,流式细胞术检测提示转染后24h-96h细胞转染率分别为52.19%、59.72%、61.43%、70.61%和62.16%,转染72h瞬时转染效率最高。收获该转染时间点细胞经RT-PCR及western blot显示,siRNA转染可有效抑制星形胶质细胞Nrf2 mRNA和蛋白水平的表达(P<0.05)。
结论成功构建Nrf2 RNA干扰表达载体并转染星形胶质细胞能有效抑制细胞Nrf2基因表达,为进一步研究Nrf2在星形胶质细胞脑缺血损伤模型中的作用提供了重要的实验材料。
目的探讨1,5-二咖啡酰奎宁酸(1,5-dicaffeoylquinic acid,1,5-diCQA)对星形胶质细胞脑缺血模型的保护作用及其可能的机制。
方法用缺糖缺氧再灌注损伤(oxygen and glucose deprivation/reperfusion, OGD/R)处理原代培养星形胶质细胞作为脑缺血的体外模型,实验分为对照组,缺血再灌注组和1,5-diCQA预处理+缺血再灌注组,根据1,5-diCQA预处理的浓度,将后者又分为5,10、20、50、100μmol/L四组。用MTT法测定各组细胞存活率,酶标仪检测细胞ROS含量和GSH水平,western blot检测各组细胞Nrf2蛋白表达水平。为验证1,5-diCQA的保护效应是否依赖于Nrf2核转位,我们又观察了1,5-diCQA预处理对缺血再灌注诱导Nrf2 siRNA组星形胶质细胞损伤的GCL活性、细胞存活率和GSH含量的干预作用。
结果星形胶质细胞经缺血再灌注损伤后,与正常对照组相比,细胞存活率下降,ROS生成增多,GSH耗竭(P<0.05)；不同浓度的1,5-diCQA预处理可以减轻缺血再灌注导致的细胞损伤,且在一定范围内具有量-效关系；50μmol/L的1,5-diCQA预处理可以显著增加缺血再灌注星形胶质细胞的Nrf2核转位和GCL活性；上述保护效应不见于Nrf2 siRNA组星形胶质细胞。
结论1,5-diCQA能改善缺血再灌注诱导的星形胶质细胞氧化应激损伤和细胞死亡,该效应依赖于1,5-diCQA对Nrf2核转位的促进作用。
目的持续性缺糖缺氧(oxygen-glucose deprivation, OGD)处理原代培养星形胶质细胞以模拟脑缺血损伤,观察细胞能量变化及死亡途径并探讨其相关机制。
方法将原代星形胶质细胞分为对照组、OGD组、100μmol/L PD150606预处理+OGD组。分别观察各组星形胶质细胞形态学变化,能量代谢变化,胀亡和凋亡百分比,western blot方法观测各组细胞paxillin、vinculin、vimentin及GFAP四种细胞骨架蛋白表达水平。
结果电镜显示OGD导致细胞出现凋亡和胀亡；OGD使细胞ATP水平呈时间依赖性下降,而凋亡和胀亡细胞比例增高,OGD处理4小时,ATP水平下降低于正常值的35%,此时胀亡成为星形胶质细胞主要死亡途径；持续OGD使星形胶质细胞paxillin、vinculin、vimentin表达逐渐减少,而GFAP先增多后减少,calpain抑制剂PD150606预处理能减少OGD导致的上述蛋白降解,并延迟细胞胀亡。
结论持续性OGD损伤可导致星形胶质细胞凋亡和胀亡；当细胞ATP耗竭到一定阈值(正常值的35%)以下,细胞主要经胀亡途径死亡；calpain调节的细胞骨架蛋白水解参与星形胶质细胞胀亡。
Objective To investigate the expression and the effect of NF-E2-related factor2 on oxidative stress in astrocytes induced by ischemia/reperfusion.
Methods Oxygen-glucose-deprivation and (OGD)/reperfusion to induce the injury of primary cultured rat astrocytes, and ROS level, cellular GSH content, changes of survival rate and the expression of Nrf2 in cytoplasm and nucleus were observed respectively.
Results With the prolongation of OGD/reperfusion, the cellular ROS level was gradually increased, GSH content was delption and the cell viability was decreased. However, at the early stage of injury (reperfusion 0.5h), the expression of Nrf2 was decreased in cytoplasm but increased in nuclear. With the injury continuing, Nrf2 in both cytoplasm and nuclear were decreased. After 12h reperfusion, the expression of Nrf2 showed a tendency toward stabilization.
Conclusion The Nrf2 nuclear translocation possessed correlation with the oxidative stress in astrocytes induced by OGD/reperfusion.
Objective To identify the effect of Nrf2 siRNA transfaction in astrocytes for the silenceof target gene.
Methods The small interfering RNA specific targeted to Nrf2 gene was constructed by chemical synthesis and was transfected into primary culture astrocytes using lipofectamine2000. Transfection efficiency was detected using fluorescence microscopy ans flow cytometry. The expression of Nrf2 mRNA and protein in the tansfected astrocytes was identified by RT-PCR and western blot analysis respectively.
Results The eukaryotic expression vector of Nrf2 was constructed and tansfected primary culture astrocytes. The transfection efficiency was 52.19%、59.72%、61.43%、 70.61% and 62.16% respectively in 24,48,72 and 96h. RT-PCR and western blot analysis showed that Nrf2 siRNA can efficiently suppress Nrf2 mRNA and protein expression (P＜0.05).
Conclusions Transfect Nrf2 siRNA into astrocytes can effectively inhibite Nrf2 mRNA and protein expression, prepare a condition for subsequent research of medical intervention in ischemia model of astrocytes.
Objective To investigate the protective effects of 1,5-diCQA preconditioning on the injury of astrocytes induced by OGD/reperfusion and the related mechanisms.
Methods Oxygen-glucose-deprivation and (OGD)/reperfusion to induce the injury of primary cultured rat astrocytes. The cells were divided into:the control group, OGD/reperfusion group,1,5-diCQA+OGD/reperfusion group. The release of LDH, ROS level, cellular GSH content, changes of survival rate and the expression of Nrf2 in cytoplasm and nucleus, glutamate-cysteine ligase (GCL) activity were observed respectively. The indicators mentioned above were also detected in Nrf2 siRNA tansfected astrocytes to verificated whether the protective effects of 1,5-diCQA depend on the activation of Nrf2/ARE pathway.
Results 1,5-diCQA pretreatment significantly suppressed cell death, reduced the production of reactive oxygen species, prevented glutathione (GSH) depletion, increased the activity of glutamate-cysteine ligase (GCL) and triggered Nrf2 nuclear translocation in astrocytes induced by 4 h OGD and 24 h reperfusion. Interestingly, these protective effects were greatly attenuated in Nrf2 siRNA-transfected cells.
Conclusions 1,5-diCQA has antioxidant signaling properties that upregulate GSH synthesis by stimulating the Nrf2 pathway in astrocytes and protects them from cell death in an in vitro model of ischemia/reperfusion.
Objective To study the effect of persistent oxygen-glucose-deprivation (OGD) on the death pathway of primary culture rat astrocytes and the relevant mechanisms.
Methods The primary culture rat astrocytes were divided into three groups:①the control group:cells maintained in high glucose DMEM supplemented with 20% fetal calf serum;②the cells treated with OGD;③pretreatment with PD 150606 (100μmol/L) before OGD. the changes of the cellular morphology, the energy metabolism of astrocytes, and the percentages of apoptosis or oncosis of the astrocytes induced by OGD were observed respectively, and Western blot was adoped to assay the protein expression of several cytoskeletal proteins, including paxillin, vinculin, vimentin and GFAP.
Results Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and oncosis in individual cells. The cellular ATP content was gradually decreased (P＜0.05) and the percentages of apoptotic and oncotic cells were increased over the OGD time(P＜0.05). After 4 h OGD, the ATP depletion below 35% of control and oncosis became the main pathway of astrocytes death. OGD led to a significant decrease in paxillin, vinculin, vimentin protein levels in a time-dependent manner (P<0.05) while GFAP appeared markedly more than the control at 0.5 h OGD treatment (P＜0.05), then decreased later. Pre-treatment with 100μmol/L Calpain inhibitor PD150606 led to decrease in the loss of cytoskeleton-associated proteins, and delayed the LDH release of astrocytes associated OGD damage.
Conclusion Astrocytes induced by persistent OGD would be go though apoptosis and oncosis, and there was a narrow range of ATP threshold (<35%of the control) that determines astrocytes oncotic death induced by persistent OGD; calpain-mediated hydrolysis of the cytoskeleton-associated proteins may contribute to astrocytes oncosis.
引文
1. 中华医学会神经病学分会脑血管病学组急性缺血性脑卒中诊治指南撰写组.中国急性缺血性脑卒中诊治指南2010.中华神经科杂志.2010,43：1-8.
2. Lee SR, Lo EH. Interactions between p38 mitogen-activated protein kinase and caspase-3 in cerebral endothelial cell death after hypoxia-reoxygenation. Stroke.2003; 34(11):2704-2709.
3. del Zoppo GJ. Stroke and neurovascular protection. N Engl J Med.2006; 9; 354:553-555.
4. Hansson E. Astroglia from defined brain regions as studied with primary cultures. Prog Neurobiol. 1988; 30:369-397.
5. Yu AC, Lau LT. Expression of interleukin-1 alpha,tnmor necrosis factor alpha and interleukin-6 genes in astrocytes under ischemic injury. Neurochem Int.2000; 36:369-377.
6. Ramos-Gomez M, Dolan PM, Itoh K, et al. Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice. Carcinogenesis.2003; 24:461-467.
7. Innamorato NG, Rojo AI, Garcia-Yague AJ. et al The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol.2008; 181:680-689.
8. Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats:the role of transcriptional factor Nrf2 and MAPK signaling pathway. Biogerontology.2007; 8:71-80.
9. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol.2000; 163:39-45.
10. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol.2000; 163:39-45.
11. Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem.2009; 284:13291-13295.
12. Moi P, Chan K, Asunis I. et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A.1994; 91:9926-9930.
13. Motohashi H, Shavit JA, Igarashi K. et al. The world according to Maf. Nucleic Acids Res.1997; 25: 2953-2959.
14. Narhi LO, Fulco AJ. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J Biol Chem.1986; 261:7160-7169.
15. Zhang DD, Hannink M. Distinct cysteine residues in Keapl are required for Keapl-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol.2003; 23:8137-8151.
16. Corbett M, Bogers WM, Heeney JL. et al. Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic. Proc Natl Acad Sci U S A.2008; 105:2046-2051.
17. Sherratt PJ, Huang HC, Nguyen T, Pickett CB. Role of protein phosphorylation in the regulation of NF-E2-related factor 2 activity. Methods Enzymol.2004; 378:286-301.
18. Shah ZA, Li RC, Thimmulappa RK, et al. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience.2007; 147:53-59.
19. Zhao J, Moore AN, Redell JB, et al Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci.2007; 27:10240-10248.
20. Wang J, Fields J, Zhao C, et al Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic Biol Med.2007; 43:408-414.
21. Kode A, Rajendrasozhan S, Caito S. et al. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol.2008; 294:L478-488.
22. Long J, Gao H, Sun L, Liu J. et al. Grape extract protects mitochondria from oxidative damage and improves locomotor dysfunction and extends lifespan in a Drosophila Parkinson's disease model. Rejuvenation Res.2009; 12:321-331.
23. Xue M, Qian Q, Adaikalakoteswari A. et al. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes.2008; 57:2809-2817.
24. Singh SV, Srivastava SK, Choi S. et al. Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem.2005; 280:19911-19924.
25. Danilov CA, Chandrasekaran K, Racz J. et al. Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation. Glia.2009; 57:645-656.
26. Kalonia H, Kumar P, Kumar A. et al. Effects of caffeic acid, rofecoxib, and their combination against quinolinic acid-induced behavioral alterations and disruption in glutathione redox status. Neurosci Bull.2009; 25:343-352.
27. Tolra R, Barcelo J, Poschenrieder C. Constitutive and aluminium-induced patterns of phenolic compounds in two maize varieties differing in aluminium tolerance. J Inorg Biochem.2009; 103: 1486-1490.
28. Park KH, Park M, Choi SE. et al. The anti-oxidative and anti-inflammatory effects of caffeoyl derivatives from the roots of Aconitum koreanum R. RAYMOND. Biol Pharm Bull.2009; 32: 2029-2033.
29. Han EH, Kim JY, Kim HG et al. Inhibitory effect of 3-caffeoyl-4-dicaffeoylquinic acid from Salicornia herbacea against phorbol ester-induced cyclooxygenase-2 expression in macrophages. Chem Biol Interact.2010; 183:397-404.
30. Cho ES, Jang YJ, Hwang MK. et al. Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals. Mutat Res.2009; 661:18-24.
31. Zhu XF, Zhang HX, Lo R. Three di-O-caffeoylquinic acid derivatives from the heads of Cynara scolymus L. Nat Prod Res.2009; 23:527-532.
32. Kim SS, Park RY, Jeon HJ. et al. Neuroprotective effects of 3,5-dicaffeoylquinic acid on hydrogen peroxide-induced cell death in SH-SY5Y cells. Phytother Res.2005; 19:243-245.
33. Chu X, Fu X, Zou L. et al. Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia. Brain Res.2007; 1149:157-164.
34. Trump BF, Berezesky IK, Chang SH, et al. The pathways of cell death:oncosis, apoptosis, and necrosis. Toxicol Pathol.1997; 25:82-88.
35. Liu X, Van VT, Schnellmann RG. The role of calpain in oncotic cell death. Annu Rev Pharmacol Toxicol.2004; 44:349-370.
36. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J. Physiol Renal Physiol.1998; 274:F315-327.
37. Liu XL, Schnellmann RG. Calpain Mediates Progressive Plasma Membrane Permeability and Proteolysis of Cytoskeleton-Associated Paxillin, Talin, and Vinculin during Renal Cell Death. J Pharmacol Exp Ther.2003; 304:63-70.
38. Elliget KA, Phelps PC, Trump BF. Cytosolic Ca2Celevation and calpain inhibitors in HgC12 injury to rat kidney proximal tubule epithelial cells. Pathobiology.1994; 62:298-310.
1. Schaller B. Prospects for the future:the role of free radicals in the treatment of stroke. Free Radic Biol Med.2005 15;38(4):411-25.
2. Zhang W, Stanimirovic D. Current and future therapeutic strategies to target inflammation in stroke. Curr Drug Targets Inflamm Allergy.2002; 1 (2):151-66.
3. Pisani A, Bonsi P, Calabresi P. Calcium signaling and neuronal vulnerability to ischemia in the striatum.Cell Calcium.2004; 36 (3-4):277-84.
4. De Cristobal J, Cardenas A, Lizasoain I, et al. Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen-glucose deprivation. Stroke.2002; 33 (1):261-7.
5. Margaill I, Plotkine M, Lerouet D. Antioxidant strategies in the treatment of stroke. Free Radic Biol Med.2005; 39(4):429-43.
6. Temple S. The development of neural stem cells [J]. Nature,2001,414 (6859):112-117.
7. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain[J]. FASEB J, 1995,9(7):526-533.
8. Moi P, Chan K, Asunis I, et al Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region [J]. Proc Natl Acad Sci U S A,1994,91 (21):9926-9930.
9. Juurlink BH, Hertz L, Yager JY. Astrocyte maturation and susceptibility to ischaemia or substrate deprivation [J]. Neuroreport,1992,3 (12):1135-1137.
10. Shah ZA, Li RC, Thimmulappa RK, et al Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury [J]. Neuroscience,2007,147 (1):53-59.
11. Zhao J, Moore AN, Redell JB, et al Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury [J]. J Neurosci,2007,27(38):10240-10248.
12. Wang J, Fields J, Zhao C, et al Role of Nrf2 in protection against intracerebral hemorrhage injury in mice [J]. Free Radic Biol Med,2007,43 (3):408-414.
13. Keelan J, Bates TE, Clark JB. Heightened resistance of the neonatal brain to ischemia-reperfusion involves a lack of mitochondrial damage in the nerve terminal [J]. Brain Res,1999,821 (1):124-133.
14. Heiss WD, Graf R, Wienhard K, et al Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats [J]. J Cereb Blood Flow Metab,1994,14 (6):892-902.
15. Ramos-Gomez M, Dolan PM, Itoh K, et al Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice [J]. Carcinogenesis,2003,24 (3):461-467.
16. Innamorato NG, Rojo AI, Garcia-Yague AJ, et al The transcription factor Nrf2 is a therapeutic target against brain inflammation[J]. J Immunol,2008,181 (1):680-689.
17. Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats:the role of transcriptional factor Nrf2 and MAPK signaling pathway [J]. Biogerontology,2007,8 (2):71-80.
18. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia [J]. Exp Neurol,2000,163 (1):39-45.
1. Brantl S. Antisense-RNA regulation and RNA interference. Biochim Biophys Acta.2002; 1575: 15-25.
2. Semizarov D, Kroeger P, Fesik S. siRNA-mediated gene silencing:a global genome view. Nucleic Acids Res.2004; 32:3836-3845.
3. Z.H. Chen, Y. Yoshida, Y. Saito, A. Sekine, N. Noguchi, E. Niki, Induction of adaptive response and enhancement of PC 12 cell tolerance by 7-hydroxycholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms, J. Biol. Chem.281 (2006) 14440-14445.
4. H. Usami, Y. Kusano, T. Kumagai. et al. Selective induction of the tumor marker glutathione
S-transferase P1 by proteasome inhibitors, J. Biol. Chem.2005; 280:25267-25276.
5. Narhi LO, Fulco AJ. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J Biol Chem.1986; 261:7160-7169.
6. Zhang DD, Hannink M. Distinct cysteine residues in Keapl are required for Keapl-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol.2003; 23:8137-8151.
7. Corbett M, Bogers WM, Heeney JL. et al. Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic. Proc Natl Acad Sci U S A.2008; 105:2046-2051.
8. Fire A, Xu S, Montgomery MK. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature.1998; 391:806-811.
9. Winston WM, Molodowitch C, Hunter CP. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science.2002; 295:2456-2459.
10. Kawasaki H, Taira K. Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells. Nucleic Acids Res.2003; 31:700-707.
11. Caplen NJ, Fleenor J, Fire A. et al. dsRNA-mediated gene silencing in cultured Drosophila cells:a tissue culture model for the analysis of RNA interference. Gene.2000; 252:95-105.
12. Elbashir SM, Harborth J, Lendeckel W. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature.2001; 411:494-498.
13. Harborth J, Elbashir SM, Bechert K. et al. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci.2001; 114:4557-4565.
14. Nagy P, Arndt-Jovin DJ, Jovin TM. Small interfering RNAs suppress the expression of endogenous and GFP-fused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1-overexpressing cells. Exp Cell Res.2003; 285:39-49.
15. Thimmulappa RK, Mai KH, Srisuma S. et al. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res.2002; 62: 5196-5203.
16. Kwak MK, Wakabayashi N, Itoh K. et al. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keapl-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem.2003; 278:8135-8145.
17. Chan K, Han XD, Kan YW. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci U S A.2001; 98:4611-4616.
1. B. Pfeiffer-Guglielmi, B. Fleckenstein, G. Jung, B. Hamprecht, Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies, J. Neurochem.85 (2003) 73-81.
2. G.A. Dienel, L. Hertz, Astrocytic contributions to bioenergetics of cerebral ischemia, Glia.50 (2005) 362-88.
3. B.H. Juurlink, Response of glial cells to ischemia:roles of reactive oxygen species and glutathione, Neurosci. Biobehav. Rev.21 (1997) 151-166.
4. Y.B. Ouyang, R.G. Giffard, Changes in astrocyte mitochondrial function with stress:effects of Bcl-2 family proteins, Neurochem. Int.45 (2004) 371-379.
5. R.E. Haskew-Layton, A.A. Mongin, H.K. Kimelberg, Hydrogen peroxide potentiates volume-sensitive excitatory amino acid release via a mechanism involving Ca2+/calmodulin-dependent protein kinase Ⅱ, J. Biol. Chem.280 (2005) 3548-3554.
6. X. Sun, H. Erb, T.H. Murphy, Coordinate regulation of glutathione metabolism in astrocytes by Nrf2, Biochem. Biophys. Res. Commun.326 (2005) 371-377.
7. L. Fisk, N.N. Nalivaeva, J.P. Boyle, C.S. Peers, A.J. Turner, Effects of hypoxia and oxidative stress on expression of neprilysin in human neuroblastoma cells and rat cortical neurones and astrocytes, Neurochem. Res.32 (2007) 1741-1748.
8. T. Nguyen, P.J. Sherratt, C.B. Pickett, Regulatory mechanisms controlling gene expression mediated by the antioxidant response element, Annu. Rev. Pharmacol. Toxicol.43 (2003) 233-260.
9. L.V. Favreau, C.B. Pickett, The rat quinone reductase antioxidant response element. Identification of the nucleotide sequence required for basal and inducible activity and detection of antioxidant response element-binding proteins in hepatoma and non-hepatoma cell lines, J. Biol. Chem.270 (1995) 24468-24474.
10. R.T. Mulcahy, J.J. Gipp, Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene, Biochem. Biophys. Res. Commun.209 (1995) 227-233.
11. T. Prestera, P. Talalay, J. Alam, Y.I. Ahn, P.J. Lee, A.M. Choi, Parallel induction of heme oxygenase-1 and chemoprotective phase 2 enzymes by electrophiles and antioxidants:regulation by upstream antioxidant-responsive elements (ARE), Mol Med.1 (1995) 827-837.
12. T.M. Hung, M. Na, P.T. Thuong, N.D. Su, D. Sok, K.S. Song, Y.H. Seong, K. Bae, Antioxidant activity of caffeoyl quinic acid derivatives from the roots of Dipsacus asper Wall, J. Ethnopharmacol. 108(2006)188-192.
13. J.B. Park,5-Caffeoylquinic acid and caffeic acid orally administered suppress P-selectin expression on mouse platelets, J. Nutr. Biochem.20 (2009) 800-805.
14. R. Ciccarelli, I. D'Alimonte, C. Santavenere, M. D'Auro, P. Ballerini, E. Nargi, S. Buccella, S. NicosiaFolco, F. Caciagli, P. Di. Iorio, Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway, Eur. J. Neurosci.20 (2004) 1514-1524.
15. Bondarenko, M. Chesler, Rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular ion shifts, Glia.34 (2001) 134-142.
16. M.P. Goldberg, J.H. Weiss, P.C. Pham, D.W. Choi, N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture, J. Pharmacol. Exp. Ther.243 (1987) 784-791.
17. S.K. Kim, J.W. Yang, M.R. Kim, S.H. Roh, H.G. Kim, K.Y. Lee, H.G. Jeong, K.W. Kang, Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in tamoxifen-resistant breast cancer cells, Free Radic Biol Med.45 (2008) 537-546.
18. D. Toroser, R.S. Sohal, Kinetic characteristics of native gamma-glutamylcysteine ligase in the aging housefly, Musca domestica L, Biochem. Biophys. Res. Commun.326 (2005) 586-593.
19. Z.H. Chen, Y. Yoshida, Y. Saito, A. Sekine, N. Noguchi, E. Niki, Induction of adaptive response and enhancement of PC 12 cell tolerance by 7-hydroxy cholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms, J. Biol. Chem.281 (2006) 14440-14445.
20. H. Usami, Y. Kusano, T. Kumagai, S. Osada, K. Itoh, A. Kobayashi, M. Yamamoto, K. Uchida, Selective induction of the tumor marker glutathione S-transferase P1 by proteasome inhibitors, J, Biol. Chem.280 (2005) 25267-25276.
21. P.H. Chan, Role of oxidants in ischemic brain damage, Stroke.27 (1996) 1124-1129.
22. C.A. Piantadosi, J. Zhang, Mitochondrial generation of reactive oxygen species after brain ischemia in the rat, Stroke.27 (1996) 327-331.
23. J.S. Bains, C.A. Shaw, Neurodegenerative disorders in humans:the role of glutathione in oxidative stress-mediated neuronal death, Brain Res. Rev.25 (1997) 335-358.
24. D. Liu, C.L. Smith, F.C. Barone, J.A. Ellison, P.G. Lysko, K. Li, I.A. Simpson, Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain, Mol. Brain Res.68 (1999) 29-41.
25. D.A. Dawson, D.I. Graham, J. McCulloch, I.M. Macrae, Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia, Br. J. Pharmacol.113 (1994) 247-253.
26. J.B. Schulz, J. Lindenau, J. Seyfried,. J. Dichgans, Glutathione, oxidative stress and neurodegeneration, Eur. J. Biochem.267 (2000) 4904-4911.
27. R. Dringen, Metabolism and functions of glutathione in brain, Prog. Neurobiol.62 (2000) 649-671.
28. J.C. Fernandez-Checa, C. Garcia-Ruiz, M. Ookhtens, N. Kaplowitz, Impaired uptake of glutathione by hepatic mitochondria from chronic ethanol-fed rats. Tracer kinetic studies in vitro and in vivo and susceptibility to oxidant stress, J. Clin. Invest.87 (1991) 397-405.
29. P. Moi, K. Chan, I. Asunis, A. Cao, Y.W. Kan, Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region, Proc. Natl. Acad. Sci. USA.91 (1994) 9926-9930.
30. R. Li, M.A. Bianchet, P. Talalay, L.M. Amzel, The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy:mechanism of the two-electron reduction, Proc. Natl. Acad. Sci. USA.92 (1995) 8846-8850.
31. M.F. Anderson, N.R. Sims, The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions, J. Neurochem.81 (2002) 541-549.
32. Y. Liu, J.T. Kern, J.R. Walker, J.A. Johnson, P.G. Schultz, H. Luesch, A genomic screen for activators of the antioxidant response element, Proc. Natl. Acad. Sci. USA.104 (2007) 5205-5210.
33. A.K. Jaiswal, Regulation of genes encoding NAD(P)H:quinone oxidoreductases, Free Radic. Biol. Med.29 (2000) 254-262.
1. Majno G, Joris I. Apoptosis, oncosis, and necrosis:an overview of cell death [J]. Am J Pathol,1995,
146:3-15.
2. Levin S, Bucci TJ, Cohen SM, et al. The nomenclature of cell death:recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists [J].Toxicol Pathol,1999,27:484-90.
3. Leist M, Jaattela M. Four deaths and a funeral:from caspases to alternative mechanisms [J]. Nat Rev Mol Cell Biol,2001,2:589-598.
4. Deshpande J, Bergstedt K, Linden T, et al. Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia:evidence against programmed cell death [J]. Exp Brain Res, 1992,88:91-105.
5. Colbourne F, Sutherland GR, Auer RN. Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia [J]. J Neurosci,1999,19:4200-4210.
6. Nicotera P, Lipton SA. Excitotoxins in neuronal apoptosis and necrosis [J]. J Cereb Blood Flow Metab,1999,19:583-591.
7. Otani H, Matsuhisa S, Akita Y, et al. Role of Mechanical Stress in the Form of Cardiomyocyte Death During the Early Phase of Reperfusion [J]. Circ J,2006,70:1344-1355.
8. Gujral JS, Farhood A, Jaeschke H. Oncotic necrosis and caspase-dependent apoptosis during galactosamine-induced liver injury in rats [J]. Toxicol Appl Pharmacol,2003,190:37-46.
9. Chu X, Fu X, Zou L, et al. Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia [J]. Brain Res,2007,1149:157-164.
10. Liu X, Rainey JJ, Harriman JF, et al. Calpains mediate acute renal cell death:role of autolysis and translocation [J]. Am. J. Physiol. Renal Physiol,2001,81:F728-38.
11. Liu X, Harriman JF, Schnellmann RG. Cytoprotective properties of novel nonpeptide calpain inhibitors in renal cells [J]. J Pharmacol Exp Ther,2002,302:88-94.
12. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells [J]. Am J. Physiol Renal Physiol,1998,274:F315-327.
13. Trump BF, Berezesky IK, Chang SH, et al. The pathways of cell death:oncosis, apoptosis, and necrosis [J]. Toxicol Pathol,1997,25:82-88.
14. Liu X, Van VT, Schnellmann RG. The role of calpain in oncotic cell death [J]. Annu Rev Pharmacol Toxicol,2004,44:349-370.
15. Liu XL, Schnellmann RG. Calpain Mediates Progressive Plasma Membrane Permeability and
Proteolysis of Cytoskeleton-Associated Paxillin, Talin, and Vinculin during Renal Cell Death [J]. J Pharmacol Exp Ther,2003,304:63-70.
16. Elliget KA, Phelps PC, Trump BF. Cytosolic Ca2Celevation and calpain inhibitors in HgCl2 injury to rat kidney proximal tubule epithelial cells [J]. Pathobiology,1994,62:298-310.
17. Ballerini P, Ciccarelli R, Caciagli F, et al. P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes [J]. Int J Immunopathol Pharmacol,2005, 18:417-430.
18. Ciccarelli R, D'Alimonte I, Santavenere C, et al. Cysteinylleukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway [J]. Eur J Neurosci,2004,20:1514-1524.
19. Juurlink BH, Hertz L, Yager JY. Astrocyte maturation and susceptibility to ischaemia or substrate deprivation [J]. Neuroreport,1992,3:1135-1137.
20. Yu AC, Wong HK, Yung HW, et al. In vitro ischemia-induced apoptosis in primary cultures of astrocytes [J]. Glia,2001,35:121-130.
21. Chen J, Wagner MC. Altered membrane-cytoskeleton linkage and membrane blebbing in energy-depleted renal proximal tubular cells [J]. Am J Physiol Renal Physiol,2001,280:F619-F627.
22. Winkelmann ER, Charcansky A, Faccioni-Heuser MC, et al. An ultrastructural analysis of cellular death in the CAl field in the rat hippocampus after transient forebrain ischemia followed by 2,4 and 10 days of reperfusion [J]. Anat Embryol,2006,211:423-434.
23. Zhang DW, Shao J, Lin J, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis [J]. Science,2009,325:332-336.
24. Goldmann O, Sastalla I, Wos-Oxley M, et al. Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway [J]. Cell Microbiol,2009, 11:138-155.
25. Willems L, Zatta A, Holmgren K, et al. Age-related changes in ischemic tolerance in male and female mouse hearts [J]. J Mol Cell Cardiol,2005,38:245-256.
26. Humphrey ML, Cole MP, Pendergrass JC, et al. Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH) [J]. Neurotoxicology,2005,26:407-416.
27. Sims, NR. Selective impairment of respiration in mitochondria isolated from brain subregions
following transient forebrain ischemia in the rat [J]. J Neurochem,1991,56:1836-1844.
28. Leist M, Single B, Castoldi AF, et al. Intracellular adenosine triphosphate (ATP) concentration:a switch in the decision between apoptosis and necrosis [J]. J Exp Med,1997,185:1481-1486.
29. Eguchi Y, Srinivasan A, Tomaselli KJ, et al. ATP-dependent steps in apoptotic signal transduction [J]. Cancer Res,1999,59:2174-2181.
30. Shao Y, McCarthy KD. Regulation of astroglial responsiveness to neuroligands in primary culture [J]. Neuroscience,1993,55:991-1001.
31. Klein RS, Fricker LD. Heterogeneous expression of carboxypeptidase E and proenkephalin mRNAs by cultured astrocytes [J]. Brain Res,1992,569:300-310.
32. Matthias K, Kirchhoff F, Seifert G, et al. Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus [J]. J Neurosci,2003,23:1750-1758.
33. Huang YH, Bergles DE. Glutamate transporters bring competition to the synapse [J]. Curr Opin Neurobiol,2004,14:346-352.
34. Zhu Z, Zhang Q, Yu Z, et al. Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo [J]. Glia,2007,55:546-558.
35. Takayama Y, Tanaka S, Nagai K, et al. Adenovirus-mediated overexpression of C-terminal Src kinase (Csk) in type Ⅰ astrocytes interferes with cell spreading and attachment to fibronectin. Correlation with tyrosine phosphorylations of paxillin and FAK [J]. J Biol Chem,1999,274:2291-2297.
36. Jing R, Pizzolato G, Robson RM, et al. Intermediate filament protein synemin is present in human reactive and malignant astrocytes and associates with ruffled membranes in astrocytoma cells [J]. Glia, 2005,50:107-120.
37. Lepekhin EA, Eliasson C, Berthold CH, et al. Intermediate filaments regulate astrocyte motility [J]. J Neurochem,2001,79:617-625.
38. Takemura M, Gomi H, Colucci-Guyon E, et al. Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice [J]. J Neurosci,2002,22:6972-6979.
39. Neary JT, Baker L, Jorgensen SL, et al. Extracellular ATP induces stellation and increases glial fibrillary acidic protein content and DNA synthesis in primary astrocyte cultures [J]. Acta Neuropathol,1994,87:8-13.
40. Nicchia GP, Rossi A, Mola MG, et al. Actin cytoskeleton remodeling governs aquaporin-4 localization in astrocytes [J]. Glia,2008,56:1755-1766.
41. Ren QG, Yu Y, Pan DJ, et al. Lactacystin Stimulates Stellation of Cultured Rat Cortical Astrocytes [J]. Neurochem Res,2009,34:859-866.
42. Wang LP, Cheung G, Kronenberg G, et al. Mild brain ischemia induces unique physiological properties in striatal astrocytes [J]. Glia,2008,59:925-934.
43. Cataldo AM, Broadwell RD. Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. Ⅱ. Choroid plexus and ependymal epithelia, endothelia and pericytes [J]. J Neurocytol,1986,15:511-524.
44. Pellegri G, Rossier C, Magistretti PJ, et al. Cloning, localization and induction of mouse brain glycogen synthase [J]. Brain Res Mol Brain Res,1996,38:191-199.
45. Pfeiffer-Guglielmi B, Fleckenstein B, Jung G, et al. Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies [J]. J Neurochem, 2003,85:73-81.
46. Jaeschke H, Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury [J]. Gastroenterology,2003,125:1246-1257.
47. Xue DB, Zhang WH, Yun XG, et al. Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats [J]. Chin Med J,2007,120:690-695.
1. Chance, B., Sies, H. and Boveris, A. Hydroperoxide metabolism in mammalian organs. Physiological Reviews.1979; 59:527-605
2. 2 Palmer, R.M.J., Rees, D.D., Ashton, D.S. and Moncada, S. L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium dependent relaxation. Biochemical and Biophysical Research Communications.1988;153:1251-1256
3. 4 Gutteridge, J.M. and Halliwell, B. Free radicals and antioxidants in the year 2000. A historical look to the future. Annals of the New York Academy of Science.2000; 899:136-147
4. Goodall, E.F. and Morrison, K.E. Amyotrophic lateral sclerosis (motor neuron disease):proposed mechanisms and pathways to treatment. Expert Reviews in Molecular Medicine.2006; 8:1-22
5. Halliwell, B. Oxidative stress and neurodegeneration:where are we now? Journal of Neurochemistry. 2006; 97:1634-1658
6. Lin, M.T. and Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature.2006; 443:787-795
7. Browne, S.E. and Beal, M.F. Oxidative damage in Huntington's disease pathogenesis. Antioxidants and Redox Signalling.2006; 8:2061-2073
8. Moi, P., Chan, K., Asunis, I. et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proceedings of the National Academy of Sciences of the United States of America.1994; 91:9926-9930
9. Rushmore, T.H. and Pickett, C.B. Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. Journal of Biological Chemistry.1990; 265:14648-14653
10. Andrews, N.C., Erdjument-Bromage, H., Davidson, M.B. et al. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein Nature.1993; 362:722-728
11. Itoh, K., Chiba, T., Takahashi, S. et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and Biophysical Research Communications.1997; 236:313-322
12. Wakabayashi, N., Itoh, K., Wakabayashi, J. et al. Keapl-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nature Genetics.2003; 35:238-245
13. Stewart, D., Killeen, E., Naquin, R. et al. Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium. Journal of Biological Chemistry.2003; 278:2396-2402
14. McMahon, M., Thomas, N., Itoh, K. et al. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism:a two-site interaction model
for the Nrf2-Keapl complex. Journal of Biological Chemistry.2006; 281:24756-24768
15. Dinkova-Kostova, A.T., Holtzclaw, W.D., Cole, R.N. et al. Direct evidence that sulfhydryl groups of Keapl are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proceedings of the National Academy of Sciences of the United States of America.2002; 99: 11908-11913
16. Zhang, D.D. and Hannink, M. Distinct cysteine residues in Keapl are required for Keapl-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Molecular and Cellular Biology.2003; 23:8137-8151
17. Kobayashi, M. and Yamamoto, M. Nrf2-Keapl regulation of cellular defense Mechanismsagainstelectrophilesandreactiveoxygen species. Advances in Enzyme Regulation.2006; 46:113-140
18. Vargas, M.R., Pehar, M., Cassina, P. et al. Fibroblast growth factor-1 induces heme oxygenase-1 via nuclear factor erythroid 2-related factor 2 (Nrf2) in spinal cord astrocytes:consequences for motor neuron survival. Journal of Biological Chemistry.2005; 280:25571-25579
19. Tenhunen, R., Marver, H.S. and Schmid, R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America.1968; 61:748-755
20. Maines, M.D. Heme oxygenase:function, multiplicity, regulatory mechanisms, and clinical applications. The FASEB Journal.1988; 2:2557-2568
21. Shibahara, S.,Mu" ller,R., Taguchi,H. andYoshida, T. Cloningandexpressionof cDNAfor rat heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America.1985; 82:7865-7869
22. Maines, M.D., Trakshel, G.M. and Kutty, R.K. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. Journal of Biological Chemistry.1986; 261:411-419
23. Baranano, D. E. and Snyder, S.H. Neural roles for heme oxygenase:contrasts to nitric oxide synthase. Proceedings of the National Academy of Sciences of the United States of America.2001; 98: 10996-11002
24. Dwyer, B.E., Nishimura, R.N. and Lu, S.Y. Differential expression of heme oxygenase-1 in cultured cortical neurons and astrocytes determined by the aid of a new heme oxygenase antibody. Response to oxidative stress. Brain Research Molecular Brain Research.1995; 30:37-47
25. Stocker, R., Yamamoto, Y., McDonagh, A.F. et al. Bilirubin is an antioxidant of possible physiological importance. Science.1987; 235:1043-1046
26. Ferris, C.D., Jaffrey, S.R., Sawa, A. et al. Haem oxygenase-1 prevents cell death by regulating cellular iron. Nature Cell Biology.1999; 1:152-157
27. Schipper, H.M. Brain iron deposition and the free radical-mitochondrial theory of ageing. Ageing Research Reviews.2004; 3:265-301
28. Ferrante, R.J., Shinobu, L.A., Schulz, J.B. et al. Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Annals of Neurology.1997; 42: 326-334
29. Ho, Y.S., Magnenat, J.L., Bronson, R.T. et al. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. Journal of Biological Chemistry. 1997; 272:16644-16651
30. Dringen, R., Pawlowski, P.G. and Hirrlinger, J. Peroxide detoxification by brain cells. Journal of Neuroscience Research.2005; 79:157-165
31. Cole, S.P. and Deeley, R.G. Transport of glutathione and glutathione conjugates by MRP1. Trends in Pharmacological Sciences.2006; 27:438-446
32. Meister, A. Glutathione metabolism and its selective modification. Journal of Biological Chemistry. 1988;263:17205-17208
33. Moinova, H.R. and Mulcahy, R.T. Up-regulation of the human gammaglutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element. Biochemical and Biophysical Research Communications.1999; 261:661-668
34. Sasaki, H., Sato, H., Kuriyama-Matsumura, K. et al. Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. Journal of Biological Chemistry.2002; 277:44765-44771
35. Thimmulappa, R.K., Lee, H., Rangasamy, T. et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. Journal of Clinical Investigation.2006; 116:
984-995
36. Suh, J.H., Shenvi, S.V., Dixon, B.M. et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proceedings of the National Academy of Sciences of the United States of America.2004;101:3381-3386
37. Morito, N., Yoh, K., Itoh, K. et al. Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels. Oncogene.2003; 22:9275-9281
38. Pehar, M., Vargas, M.R., Robinson, K.M. et al. Mitochondrial superoxide production and nuclear factor erythroid 2-related factor 2 activation in p75 neurotrophin receptor-induced motor neuron apoptosis. Journal of Neuroscience.2007; 27:7777-7785
39. Drukarch, B., Schepens, E., Jongenelen, C.A. et al. Astrocyte-mediated enhancement of neuronal survival is abolished by glutathione deficiency. Brain Research.1997; 770:123-130
40. Sagara, J., Miura, K. and Bannai, S. Cystine uptake and glutathione level in fetal brain cells in primary culture and in suspension. Journal of Neurochemistry.1993; 61:1667-1671
41. Lee, J.M., Calkins, M.J., Chan, K. et al. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. Journal of Biological Chemistry.2003; 278:12029-12038
42. Shih, A.Y., Johnson, D.A., Wong, G., Kraft, A.D., Jiang, L., Erb, H., Johnson, J.A. and Murphy, T.H. Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. Journal of Neuroscience.2003; 23:3394-3406
43. Guo, N. and Shaw, C. Characterization and localization of glutathione binding sites on cultured astrocytes. Brain Research Molecular Brain Research.1992; 15:207-215
44. Dringen, R., Pfeiffer, B. and Hamprecht, B. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. Journal of Neuroscience.1999; 19:562-569
45. Hirrlinger, J., Ko"nig, J., Keppler, D. et al. The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress. Journal of Neurochemistry. 2001;76:627-636
46. Dringen, R., Kranich, O. and Hamprecht, B. The gamma-glutamyl transpeptidase inhibitor acivicin preserves glutathione released by astroglial cells in culture. Neurochemical Research.1997; 22:
727-733
47. Van Muiswinkel, F.L. and Kuiperij, H.B. The Nrf2-ARE Signalling pathway:promising drug target to combat oxidative stress in neurodegenerative disorders. Current Drug TargetsCNSand Neurological Disorders.2005; 4:267-281
48. Lewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma.2000; 17:871-90.
49. Kontos HA.Oxygen radicals in cerebral ischemia:the 2001 Willis lecture. Stroke.2001; 32:2712-6.
50. Althaus JS, Andrus PK, Williams CM, VonVoigtlander PF, Cazers AR, Hall ED. The use of salicylate hydroxylation to detect hydroxyl radical generation in ischemic and traumatic brain injury. Reversal by tirilazad mesylate (U-74006F). Mol Chem Neuropathol.1993; 20:147-62.
51. Bates B, Hirt L, Thomas SS, Akbarian S, Le D, Amin-Hanjani S, Whalen M, Jaenisch R, Moskowitz MA. Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress:possible involvement of oxygen free radicals. Neurobiol Dis.2002; 9:24-37.
52. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab.2001; 21:2-14.
53. Shah ZA, Li RC, Thimmulappa RK, Kensler TW, Yamamoto M, Biswal S, Dore S. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience.2007;147: 53-59.
54. Shih AY, Li P, Murphy TH. A small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo. J Neurosci.2005; 25:10321-10335.
55. Danilov CA, Chandrasekaran K, Racz J, et al. Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation. Glia.2009; 57(6):645-56.
56. Rosen, D.R., Siddique, T., Patterson, D. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature.1993; 362:59-62
57. Manfredi, G. and Xu, Z. Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. Mitochondrion.2005; 5:77-87
58. Boille'e, S., Yamanaka, K., Lobsiger, C.S. et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science.2006; 312:1389-1392
59. Este'vez, A.G., Spear, N., Manuel, S.M. et al. Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. Journal of Neuroscience.1998;18:923-931
60.134 Sarlette, A., Krampfl, K., Grothe, C. et al. Nuclear erythroid 2-related factor 2-antioxidative response element signaling pathway in motor cortex and spinal cord in amyotrophic lateral sclerosis. Journal of Neuropathology and Experimental Neurology.2008; 67:1055-1062
61. Ferraiuolo, L., Heath, P.R., Holden, H. et al. Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. Journal of Neuroscience.2007; 27:9201-9219
62. Nagai, M., Re, D.B., Nagata, T. et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nature Neuroscience.2007; 10:615-622
63. Thomas, B. and Beal, M.F. Parkinson's disease. Human Molecular Genetics.2007; 16:R183-R194
64. Alam, Z.I., Daniel, S.E., Lees, A.J. et al. A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. Journal of Neurochemistry.1997; 69:1326-1329
65. Schipper, H.M. Heme oxygenase expression in human central nervous system disorders. Free Radical Biology and Medicine.2004; 37:1995-2011
66. Wruck, CJ, Claussen, M., Fuhrmann, G. et al. Luteolin protects rat PC 12 and C6 cells against MPPt induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway. Journal of Neural Transmission Suppl.2007; 72:57-67
67. Burton, N.C., Kensler, T.W. and Guilarte, T.R. In vivo modulation of the Parkinsonian phenotype by Nrf2. Neurotoxicology.2006; 27,1094-1100
68. Chen, P.C., Vargas, M.R., Pani, A.K. et al. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease:a critical role for the astrocyte. Proceedings of the National Academy of Sciences of the United States of America.2009; 106:2933-2938
1. Nonaka T, Kuwae A, Sasakawa C, Imajoh-Ohmi S. Shigella flexneri YSH6000 induces two types of cell death, apoptosis and oncosis, in the differentiated human monoblastic cell line U937. [J].FEMS Microbiol Lett.1999 May 1,174(1):89-95.
2. Majno G, Joris I.Apoptosis, oncosis, and necrosis:an overview of cell death. [J].Am J Pathol,1995, 146:3-15.
3. Levin S. Apoptosis, necrosis, or oncosis:what is your diagnosis? a report from the Cell Death Nomenclature Committee of the Society of Toxicologic Pathologists.[J]. Toxicol. Sci.1998 41: 155-156.
4. Estacion M, Schilling WP. Blockade of maitotoxin-induced oncotic cell death reveals zeiosis. [J].BMC Physiol 2002; 2:2.
5. Dacheux D,Toussaint B, Richard M, Brochier G, Croize J, Attree I. Pseudomonas aeruginosa cystic fibrosis isolates induce rapid, type Ⅲ secretion-dependent, oncosis of macrophages and polymorphonuclear neutrophils. [J]. Infect Immun,2000,68:2916-2924.
6. Elsasser A, Suzuki K, and Schaper J. Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. [J]. Mol Cell Cardiol.2000.32:711-724.
7. Ohno M, Takemura G, Misao J, Hayakawa Y, Minatoguchi S, Fujiwara T. "Apoptotic" myocytes in infarct area in rabbit hearts may be oncotic myocytes with DNA fragmentation:analysis by immunogold electron microscopy combined with In situ nick end-labeling [J].Circulation 1998; 98:. 1422-1430.
8. D.R.Hunter, R.A.Haworth. The Ca2+-induced membrane transition in mitochondria Ⅲ. Transitional Ca2+release. [J].Arch Biochem Biophys.1979 Jul,195(2):468-477.
9. G, Reed JC. Mitochondrial control of cell death. [J].Nat Med.2000,6:513-519.
10. P. Bernardi, A. Krauskopf, E. Basso, V. Petronilli, E. Blachy-Dyson, F. Di Lisa, M. Forte, The mitochondrial permeability transition from in vitro artifacts to disease target. [J]. FEBS.2006.273: 2077-2099.
11. Kass GE, Orrenius S.Calcium signaling and cytotoxicity. [J].Environ. Health. Perspect.1999; 107:25-35.
12. Lemasters JJ, Qian T, He L, J.S. Kim, S.P. Elmore, W.E. Cascio, D.A. Brenner. Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. [J]. Antioxid Redox Signal 2002;4:769-781.
13.李树清,罗海芸.缺血后适应对树鼬海马CA1区脑血流及星形胶质细胞活化的影响及可能机制.[J].中国病理生理杂志,2008,24(6)：1090-1095.
14. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. [J]. Am J Physiol Renal Physiol,1998,274:F315-F327.
15. Mills EM, Xu D, Fergusson MM, Combs CA, Xu Y and Finkel T. Regulation of Cellular Oncosis by Uncoupling Protein 2. [J]. Biol Chem.2002,277:27385-27392.
16. Oberkofler H, Iglseder B, Klein K, Unger J, Haltmayer M. associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women. [J]. Arterioscler Thromb Vasc Biol 2005, 25:604-610.
17. Holler N, Zaru R, Micheau 0, Thome M, Thome A, Attinger, S Valitutti, J.L. Bodmer, P. Schneider, B. Seed, J. Tschopp. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. [J].Nat Immunology,2000,1(6):489-495.
18. Y. Lin, S. Choksi, H.-M. Shen, Q. F. Yang, G. M. Hur, Y. S. Kim, J. H. Tran, S. A. Nedospasov, and Z.-g. Liu. Tumor necrosis factorinduced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. [J].Biol. Chem.2004,279: 10822-10828.
19. Ma F, Zhang C, Prasad KV, et al. Molecular cloning of porimin, a novel cell surface receptor mediating oncotic cell death. [J]. Proc Natl Acad Sci USA,2001,98(17):9778-9783.
20. Barros LF, Stutzin A, Calixto A, et al. Nonselective cation channels as effectors of free radical-induced rat liver cell necrosis [J]. Hepatology,2001,33 (1):114-122.
21. Cummings BS, McHowat J, Schnellmann RG. Phospholipase A (2) s in cell injury and death. [J]. J Pharmacol Exp Ther,2000,294(3):793-799.
22. Harriman JF, Liu XL, Aleo MD, et al. Endoplasmic reticulum Ca2+signaling and calpains mediate renal cell death. [J].Cell Death Differ,2002,9:734-741.
23. Krysko O, de Ridder L, and Cornelissen M. Phosphatidylserine exposure during early primary necrosis (oncosis) in JB6 cells as evidenced by immunogold labelling technique. [J]. Apoptosis 2004, 9:495-500.
24. Croall DE, DeMartino GN. Calcium-activated neutral protease (calpain) system:structure, function and regulation. [J]. Physiol Rev,1991,71(3):813-847.
25. Kern JC, Kehrer JP. Acrolein-induced cell death:a caspase-influenced decision between apoptosis and oncosisPnecrosis. [J]. Chem Biol Interact,2002,139 (1):79-95.
26. Chang SH, Phelp s PC, Berezesky IK, et al. Studies on the mechanisms and kinetics of apop tosis induced by microinjection of cytochrome c in rat kidney tubule ep ithelial cells (NRK-52E). [J]. Am J Pathol,2000,156 (2):637-649.
27. Los M, Mozoluk M, Ferrari D, et al. Activation and caspase-mediate inhibition of PARP:amolecular swithch between fibroblast necrosis and apop tosis in death recep torsignaling. [J]. Mol Biol Cell, 2002,13:978-988.
28. Bovia F, Nabili-Tehrani AC, Werner-Favre C, Barnet M, Kindler V, Zubler RH (1998) Quiescent memory B cells in human peripheral blood co-express bcl-2 and bcl-x(L) anti-apoptotic proteins at high levels. Eur J Immunol.28:4418-4423.
29. Gujral JS, Farhood A, Jaeschke H. Oncotic necrosis and caspase-dependent apoptosis during galactosamine-induced liver injury in rats. [J]. Toxicol Appl Pharmacol,2003,190 (1):37-46.
30. Ryoke T, Gu Y, Ikeda Y, et al. Apop tosis and oncosis in the early p rogression of left ventricular dysfunction in the cardiomyopathic hamster [J]. Basic Res Cardiol,2002,97 (1):65-75.
31. Rabkin SW, Kong JY. Lovastatin-induced cardiac toxicity involves both oncotic and apop totic cell death with the apoptotic component blunted by both caspase-2 and caspase-3 inhibitors [J]. Toxicol App 1 Pharmacol,2003,193 (3):346-355.
32. Willems L, Zatta A, Holmgren K, et al. Age-related changes in ischemic tolerance in male and female mouse hearts. [J]. Mol Cell Cardiol,2005,38 (2):245-256.
33. Fickert P, TraunerM, Fuchsbichler A, et al. Oncosis represents the main type of cell death in mouse models of cholestasis. [J]. Hepatol,2005,42 (3):378-385.
2. Lee SR, Lo EH. Interactions between p38 mitogen-activated protein kinase and caspase-3 in cerebral endothelial cell death after hypoxia-reoxygenation. Stroke.2003; 34(11):2704-2709.
3. del Zoppo GJ. Stroke and neurovascular protection. N Engl J Med.2006; 9; 354:553-555.
4. Hansson E. Astroglia from defined brain regions as studied with primary cultures. Prog Neurobiol. 1988; 30:369-397.
5. Yu AC, Lau LT. Expression of interleukin-1 alpha,tnmor necrosis factor alpha and interleukin-6 genes in astrocytes under ischemic injury. Neurochem Int.2000; 36:369-377.
6. Ramos-Gomez M, Dolan PM, Itoh K, et al. Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice. Carcinogenesis.2003; 24:461-467.
7. Innamorato NG, Rojo AI, Garcia-Yague AJ. et al The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol.2008; 181:680-689.
8. Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats:the role of transcriptional factor Nrf2 and MAPK signaling pathway. Biogerontology.2007; 8:71-80.
9. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol.2000; 163:39-45.
10. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol.2000; 163:39-45.
11. Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem.2009; 284:13291-13295.
12. Moi P, Chan K, Asunis I. et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A.1994; 91:9926-9930.
13. Motohashi H, Shavit JA, Igarashi K. et al. The world according to Maf. Nucleic Acids Res.1997; 25: 2953-2959.
14. Narhi LO, Fulco AJ. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J Biol Chem.1986; 261:7160-7169.
15. Zhang DD, Hannink M. Distinct cysteine residues in Keapl are required for Keapl-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol.2003; 23:8137-8151.
16. Corbett M, Bogers WM, Heeney JL. et al. Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic. Proc Natl Acad Sci U S A.2008; 105:2046-2051.
17. Sherratt PJ, Huang HC, Nguyen T, Pickett CB. Role of protein phosphorylation in the regulation of NF-E2-related factor 2 activity. Methods Enzymol.2004; 378:286-301.
18. Shah ZA, Li RC, Thimmulappa RK, et al. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience.2007; 147:53-59.
19. Zhao J, Moore AN, Redell JB, et al Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci.2007; 27:10240-10248.
20. Wang J, Fields J, Zhao C, et al Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic Biol Med.2007; 43:408-414.
21. Kode A, Rajendrasozhan S, Caito S. et al. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol.2008; 294:L478-488.
22. Long J, Gao H, Sun L, Liu J. et al. Grape extract protects mitochondria from oxidative damage and improves locomotor dysfunction and extends lifespan in a Drosophila Parkinson's disease model. Rejuvenation Res.2009; 12:321-331.
23. Xue M, Qian Q, Adaikalakoteswari A. et al. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes.2008; 57:2809-2817.
24. Singh SV, Srivastava SK, Choi S. et al. Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem.2005; 280:19911-19924.
25. Danilov CA, Chandrasekaran K, Racz J. et al. Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation. Glia.2009; 57:645-656.
26. Kalonia H, Kumar P, Kumar A. et al. Effects of caffeic acid, rofecoxib, and their combination against quinolinic acid-induced behavioral alterations and disruption in glutathione redox status. Neurosci Bull.2009; 25:343-352.
27. Tolra R, Barcelo J, Poschenrieder C. Constitutive and aluminium-induced patterns of phenolic compounds in two maize varieties differing in aluminium tolerance. J Inorg Biochem.2009; 103: 1486-1490.
28. Park KH, Park M, Choi SE. et al. The anti-oxidative and anti-inflammatory effects of caffeoyl derivatives from the roots of Aconitum koreanum R. RAYMOND. Biol Pharm Bull.2009; 32: 2029-2033.
29. Han EH, Kim JY, Kim HG et al. Inhibitory effect of 3-caffeoyl-4-dicaffeoylquinic acid from Salicornia herbacea against phorbol ester-induced cyclooxygenase-2 expression in macrophages. Chem Biol Interact.2010; 183:397-404.
30. Cho ES, Jang YJ, Hwang MK. et al. Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals. Mutat Res.2009; 661:18-24.
31. Zhu XF, Zhang HX, Lo R. Three di-O-caffeoylquinic acid derivatives from the heads of Cynara scolymus L. Nat Prod Res.2009; 23:527-532.
32. Kim SS, Park RY, Jeon HJ. et al. Neuroprotective effects of 3,5-dicaffeoylquinic acid on hydrogen peroxide-induced cell death in SH-SY5Y cells. Phytother Res.2005; 19:243-245.
33. Chu X, Fu X, Zou L. et al. Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia. Brain Res.2007; 1149:157-164.
34. Trump BF, Berezesky IK, Chang SH, et al. The pathways of cell death:oncosis, apoptosis, and necrosis. Toxicol Pathol.1997; 25:82-88.
35. Liu X, Van VT, Schnellmann RG. The role of calpain in oncotic cell death. Annu Rev Pharmacol Toxicol.2004; 44:349-370.
36. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J. Physiol Renal Physiol.1998; 274:F315-327.
37. Liu XL, Schnellmann RG. Calpain Mediates Progressive Plasma Membrane Permeability and Proteolysis of Cytoskeleton-Associated Paxillin, Talin, and Vinculin during Renal Cell Death. J Pharmacol Exp Ther.2003; 304:63-70.
38. Elliget KA, Phelps PC, Trump BF. Cytosolic Ca2Celevation and calpain inhibitors in HgC12 injury to rat kidney proximal tubule epithelial cells. Pathobiology.1994; 62:298-310.
1. Schaller B. Prospects for the future:the role of free radicals in the treatment of stroke. Free Radic Biol Med.2005 15;38(4):411-25.
2. Zhang W, Stanimirovic D. Current and future therapeutic strategies to target inflammation in stroke. Curr Drug Targets Inflamm Allergy.2002; 1 (2):151-66.
3. Pisani A, Bonsi P, Calabresi P. Calcium signaling and neuronal vulnerability to ischemia in the striatum.Cell Calcium.2004; 36 (3-4):277-84.
4. De Cristobal J, Cardenas A, Lizasoain I, et al. Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen-glucose deprivation. Stroke.2002; 33 (1):261-7.
5. Margaill I, Plotkine M, Lerouet D. Antioxidant strategies in the treatment of stroke. Free Radic Biol Med.2005; 39(4):429-43.
6. Temple S. The development of neural stem cells [J]. Nature,2001,414 (6859):112-117.
7. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain[J]. FASEB J, 1995,9(7):526-533.
8. Moi P, Chan K, Asunis I, et al Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region [J]. Proc Natl Acad Sci U S A,1994,91 (21):9926-9930.
9. Juurlink BH, Hertz L, Yager JY. Astrocyte maturation and susceptibility to ischaemia or substrate deprivation [J]. Neuroreport,1992,3 (12):1135-1137.
10. Shah ZA, Li RC, Thimmulappa RK, et al Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury [J]. Neuroscience,2007,147 (1):53-59.
11. Zhao J, Moore AN, Redell JB, et al Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury [J]. J Neurosci,2007,27(38):10240-10248.
12. Wang J, Fields J, Zhao C, et al Role of Nrf2 in protection against intracerebral hemorrhage injury in mice [J]. Free Radic Biol Med,2007,43 (3):408-414.
13. Keelan J, Bates TE, Clark JB. Heightened resistance of the neonatal brain to ischemia-reperfusion involves a lack of mitochondrial damage in the nerve terminal [J]. Brain Res,1999,821 (1):124-133.
14. Heiss WD, Graf R, Wienhard K, et al Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats [J]. J Cereb Blood Flow Metab,1994,14 (6):892-902.
15. Ramos-Gomez M, Dolan PM, Itoh K, et al Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice [J]. Carcinogenesis,2003,24 (3):461-467.
16. Innamorato NG, Rojo AI, Garcia-Yague AJ, et al The transcription factor Nrf2 is a therapeutic target against brain inflammation[J]. J Immunol,2008,181 (1):680-689.
17. Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats:the role of transcriptional factor Nrf2 and MAPK signaling pathway [J]. Biogerontology,2007,8 (2):71-80.
18. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia [J]. Exp Neurol,2000,163 (1):39-45.
1. Brantl S. Antisense-RNA regulation and RNA interference. Biochim Biophys Acta.2002; 1575: 15-25.
2. Semizarov D, Kroeger P, Fesik S. siRNA-mediated gene silencing:a global genome view. Nucleic Acids Res.2004; 32:3836-3845.
3. Z.H. Chen, Y. Yoshida, Y. Saito, A. Sekine, N. Noguchi, E. Niki, Induction of adaptive response and enhancement of PC 12 cell tolerance by 7-hydroxycholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms, J. Biol. Chem.281 (2006) 14440-14445.
4. H. Usami, Y. Kusano, T. Kumagai. et al. Selective induction of the tumor marker glutathione
S-transferase P1 by proteasome inhibitors, J. Biol. Chem.2005; 280:25267-25276.
5. Narhi LO, Fulco AJ. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J Biol Chem.1986; 261:7160-7169.
6. Zhang DD, Hannink M. Distinct cysteine residues in Keapl are required for Keapl-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol.2003; 23:8137-8151.
7. Corbett M, Bogers WM, Heeney JL. et al. Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic. Proc Natl Acad Sci U S A.2008; 105:2046-2051.
8. Fire A, Xu S, Montgomery MK. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature.1998; 391:806-811.
9. Winston WM, Molodowitch C, Hunter CP. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science.2002; 295:2456-2459.
10. Kawasaki H, Taira K. Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells. Nucleic Acids Res.2003; 31:700-707.
11. Caplen NJ, Fleenor J, Fire A. et al. dsRNA-mediated gene silencing in cultured Drosophila cells:a tissue culture model for the analysis of RNA interference. Gene.2000; 252:95-105.
12. Elbashir SM, Harborth J, Lendeckel W. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature.2001; 411:494-498.
13. Harborth J, Elbashir SM, Bechert K. et al. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci.2001; 114:4557-4565.
14. Nagy P, Arndt-Jovin DJ, Jovin TM. Small interfering RNAs suppress the expression of endogenous and GFP-fused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1-overexpressing cells. Exp Cell Res.2003; 285:39-49.
15. Thimmulappa RK, Mai KH, Srisuma S. et al. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res.2002; 62: 5196-5203.
16. Kwak MK, Wakabayashi N, Itoh K. et al. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keapl-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem.2003; 278:8135-8145.
17. Chan K, Han XD, Kan YW. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci U S A.2001; 98:4611-4616.
1. B. Pfeiffer-Guglielmi, B. Fleckenstein, G. Jung, B. Hamprecht, Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies, J. Neurochem.85 (2003) 73-81.
2. G.A. Dienel, L. Hertz, Astrocytic contributions to bioenergetics of cerebral ischemia, Glia.50 (2005) 362-88.
3. B.H. Juurlink, Response of glial cells to ischemia:roles of reactive oxygen species and glutathione, Neurosci. Biobehav. Rev.21 (1997) 151-166.
4. Y.B. Ouyang, R.G. Giffard, Changes in astrocyte mitochondrial function with stress:effects of Bcl-2 family proteins, Neurochem. Int.45 (2004) 371-379.
5. R.E. Haskew-Layton, A.A. Mongin, H.K. Kimelberg, Hydrogen peroxide potentiates volume-sensitive excitatory amino acid release via a mechanism involving Ca2+/calmodulin-dependent protein kinase Ⅱ, J. Biol. Chem.280 (2005) 3548-3554.
6. X. Sun, H. Erb, T.H. Murphy, Coordinate regulation of glutathione metabolism in astrocytes by Nrf2, Biochem. Biophys. Res. Commun.326 (2005) 371-377.
7. L. Fisk, N.N. Nalivaeva, J.P. Boyle, C.S. Peers, A.J. Turner, Effects of hypoxia and oxidative stress on expression of neprilysin in human neuroblastoma cells and rat cortical neurones and astrocytes, Neurochem. Res.32 (2007) 1741-1748.
8. T. Nguyen, P.J. Sherratt, C.B. Pickett, Regulatory mechanisms controlling gene expression mediated by the antioxidant response element, Annu. Rev. Pharmacol. Toxicol.43 (2003) 233-260.
9. L.V. Favreau, C.B. Pickett, The rat quinone reductase antioxidant response element. Identification of the nucleotide sequence required for basal and inducible activity and detection of antioxidant response element-binding proteins in hepatoma and non-hepatoma cell lines, J. Biol. Chem.270 (1995) 24468-24474.
10. R.T. Mulcahy, J.J. Gipp, Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene, Biochem. Biophys. Res. Commun.209 (1995) 227-233.
11. T. Prestera, P. Talalay, J. Alam, Y.I. Ahn, P.J. Lee, A.M. Choi, Parallel induction of heme oxygenase-1 and chemoprotective phase 2 enzymes by electrophiles and antioxidants:regulation by upstream antioxidant-responsive elements (ARE), Mol Med.1 (1995) 827-837.
12. T.M. Hung, M. Na, P.T. Thuong, N.D. Su, D. Sok, K.S. Song, Y.H. Seong, K. Bae, Antioxidant activity of caffeoyl quinic acid derivatives from the roots of Dipsacus asper Wall, J. Ethnopharmacol. 108(2006)188-192.
13. J.B. Park,5-Caffeoylquinic acid and caffeic acid orally administered suppress P-selectin expression on mouse platelets, J. Nutr. Biochem.20 (2009) 800-805.
14. R. Ciccarelli, I. D'Alimonte, C. Santavenere, M. D'Auro, P. Ballerini, E. Nargi, S. Buccella, S. NicosiaFolco, F. Caciagli, P. Di. Iorio, Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway, Eur. J. Neurosci.20 (2004) 1514-1524.
15. Bondarenko, M. Chesler, Rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular ion shifts, Glia.34 (2001) 134-142.
16. M.P. Goldberg, J.H. Weiss, P.C. Pham, D.W. Choi, N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture, J. Pharmacol. Exp. Ther.243 (1987) 784-791.
17. S.K. Kim, J.W. Yang, M.R. Kim, S.H. Roh, H.G. Kim, K.Y. Lee, H.G. Jeong, K.W. Kang, Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in tamoxifen-resistant breast cancer cells, Free Radic Biol Med.45 (2008) 537-546.
18. D. Toroser, R.S. Sohal, Kinetic characteristics of native gamma-glutamylcysteine ligase in the aging housefly, Musca domestica L, Biochem. Biophys. Res. Commun.326 (2005) 586-593.
19. Z.H. Chen, Y. Yoshida, Y. Saito, A. Sekine, N. Noguchi, E. Niki, Induction of adaptive response and enhancement of PC 12 cell tolerance by 7-hydroxy cholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms, J. Biol. Chem.281 (2006) 14440-14445.
20. H. Usami, Y. Kusano, T. Kumagai, S. Osada, K. Itoh, A. Kobayashi, M. Yamamoto, K. Uchida, Selective induction of the tumor marker glutathione S-transferase P1 by proteasome inhibitors, J, Biol. Chem.280 (2005) 25267-25276.
21. P.H. Chan, Role of oxidants in ischemic brain damage, Stroke.27 (1996) 1124-1129.
22. C.A. Piantadosi, J. Zhang, Mitochondrial generation of reactive oxygen species after brain ischemia in the rat, Stroke.27 (1996) 327-331.
23. J.S. Bains, C.A. Shaw, Neurodegenerative disorders in humans:the role of glutathione in oxidative stress-mediated neuronal death, Brain Res. Rev.25 (1997) 335-358.
24. D. Liu, C.L. Smith, F.C. Barone, J.A. Ellison, P.G. Lysko, K. Li, I.A. Simpson, Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain, Mol. Brain Res.68 (1999) 29-41.
25. D.A. Dawson, D.I. Graham, J. McCulloch, I.M. Macrae, Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia, Br. J. Pharmacol.113 (1994) 247-253.
26. J.B. Schulz, J. Lindenau, J. Seyfried,. J. Dichgans, Glutathione, oxidative stress and neurodegeneration, Eur. J. Biochem.267 (2000) 4904-4911.
27. R. Dringen, Metabolism and functions of glutathione in brain, Prog. Neurobiol.62 (2000) 649-671.
28. J.C. Fernandez-Checa, C. Garcia-Ruiz, M. Ookhtens, N. Kaplowitz, Impaired uptake of glutathione by hepatic mitochondria from chronic ethanol-fed rats. Tracer kinetic studies in vitro and in vivo and susceptibility to oxidant stress, J. Clin. Invest.87 (1991) 397-405.
29. P. Moi, K. Chan, I. Asunis, A. Cao, Y.W. Kan, Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region, Proc. Natl. Acad. Sci. USA.91 (1994) 9926-9930.
30. R. Li, M.A. Bianchet, P. Talalay, L.M. Amzel, The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy:mechanism of the two-electron reduction, Proc. Natl. Acad. Sci. USA.92 (1995) 8846-8850.
31. M.F. Anderson, N.R. Sims, The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions, J. Neurochem.81 (2002) 541-549.
32. Y. Liu, J.T. Kern, J.R. Walker, J.A. Johnson, P.G. Schultz, H. Luesch, A genomic screen for activators of the antioxidant response element, Proc. Natl. Acad. Sci. USA.104 (2007) 5205-5210.
33. A.K. Jaiswal, Regulation of genes encoding NAD(P)H:quinone oxidoreductases, Free Radic. Biol. Med.29 (2000) 254-262.
1. Majno G, Joris I. Apoptosis, oncosis, and necrosis:an overview of cell death [J]. Am J Pathol,1995,
146:3-15.
2. Levin S, Bucci TJ, Cohen SM, et al. The nomenclature of cell death:recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists [J].Toxicol Pathol,1999,27:484-90.
3. Leist M, Jaattela M. Four deaths and a funeral:from caspases to alternative mechanisms [J]. Nat Rev Mol Cell Biol,2001,2:589-598.
4. Deshpande J, Bergstedt K, Linden T, et al. Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia:evidence against programmed cell death [J]. Exp Brain Res, 1992,88:91-105.
5. Colbourne F, Sutherland GR, Auer RN. Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia [J]. J Neurosci,1999,19:4200-4210.
6. Nicotera P, Lipton SA. Excitotoxins in neuronal apoptosis and necrosis [J]. J Cereb Blood Flow Metab,1999,19:583-591.
7. Otani H, Matsuhisa S, Akita Y, et al. Role of Mechanical Stress in the Form of Cardiomyocyte Death During the Early Phase of Reperfusion [J]. Circ J,2006,70:1344-1355.
8. Gujral JS, Farhood A, Jaeschke H. Oncotic necrosis and caspase-dependent apoptosis during galactosamine-induced liver injury in rats [J]. Toxicol Appl Pharmacol,2003,190:37-46.
9. Chu X, Fu X, Zou L, et al. Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia [J]. Brain Res,2007,1149:157-164.
10. Liu X, Rainey JJ, Harriman JF, et al. Calpains mediate acute renal cell death:role of autolysis and translocation [J]. Am. J. Physiol. Renal Physiol,2001,81:F728-38.
11. Liu X, Harriman JF, Schnellmann RG. Cytoprotective properties of novel nonpeptide calpain inhibitors in renal cells [J]. J Pharmacol Exp Ther,2002,302:88-94.
12. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells [J]. Am J. Physiol Renal Physiol,1998,274:F315-327.
13. Trump BF, Berezesky IK, Chang SH, et al. The pathways of cell death:oncosis, apoptosis, and necrosis [J]. Toxicol Pathol,1997,25:82-88.
14. Liu X, Van VT, Schnellmann RG. The role of calpain in oncotic cell death [J]. Annu Rev Pharmacol Toxicol,2004,44:349-370.
15. Liu XL, Schnellmann RG. Calpain Mediates Progressive Plasma Membrane Permeability and
Proteolysis of Cytoskeleton-Associated Paxillin, Talin, and Vinculin during Renal Cell Death [J]. J Pharmacol Exp Ther,2003,304:63-70.
16. Elliget KA, Phelps PC, Trump BF. Cytosolic Ca2Celevation and calpain inhibitors in HgCl2 injury to rat kidney proximal tubule epithelial cells [J]. Pathobiology,1994,62:298-310.
17. Ballerini P, Ciccarelli R, Caciagli F, et al. P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes [J]. Int J Immunopathol Pharmacol,2005, 18:417-430.
18. Ciccarelli R, D'Alimonte I, Santavenere C, et al. Cysteinylleukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway [J]. Eur J Neurosci,2004,20:1514-1524.
19. Juurlink BH, Hertz L, Yager JY. Astrocyte maturation and susceptibility to ischaemia or substrate deprivation [J]. Neuroreport,1992,3:1135-1137.
20. Yu AC, Wong HK, Yung HW, et al. In vitro ischemia-induced apoptosis in primary cultures of astrocytes [J]. Glia,2001,35:121-130.
21. Chen J, Wagner MC. Altered membrane-cytoskeleton linkage and membrane blebbing in energy-depleted renal proximal tubular cells [J]. Am J Physiol Renal Physiol,2001,280:F619-F627.
22. Winkelmann ER, Charcansky A, Faccioni-Heuser MC, et al. An ultrastructural analysis of cellular death in the CAl field in the rat hippocampus after transient forebrain ischemia followed by 2,4 and 10 days of reperfusion [J]. Anat Embryol,2006,211:423-434.
23. Zhang DW, Shao J, Lin J, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis [J]. Science,2009,325:332-336.
24. Goldmann O, Sastalla I, Wos-Oxley M, et al. Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway [J]. Cell Microbiol,2009, 11:138-155.
25. Willems L, Zatta A, Holmgren K, et al. Age-related changes in ischemic tolerance in male and female mouse hearts [J]. J Mol Cell Cardiol,2005,38:245-256.
26. Humphrey ML, Cole MP, Pendergrass JC, et al. Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH) [J]. Neurotoxicology,2005,26:407-416.
27. Sims, NR. Selective impairment of respiration in mitochondria isolated from brain subregions
following transient forebrain ischemia in the rat [J]. J Neurochem,1991,56:1836-1844.
28. Leist M, Single B, Castoldi AF, et al. Intracellular adenosine triphosphate (ATP) concentration:a switch in the decision between apoptosis and necrosis [J]. J Exp Med,1997,185:1481-1486.
29. Eguchi Y, Srinivasan A, Tomaselli KJ, et al. ATP-dependent steps in apoptotic signal transduction [J]. Cancer Res,1999,59:2174-2181.
30. Shao Y, McCarthy KD. Regulation of astroglial responsiveness to neuroligands in primary culture [J]. Neuroscience,1993,55:991-1001.
31. Klein RS, Fricker LD. Heterogeneous expression of carboxypeptidase E and proenkephalin mRNAs by cultured astrocytes [J]. Brain Res,1992,569:300-310.
32. Matthias K, Kirchhoff F, Seifert G, et al. Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus [J]. J Neurosci,2003,23:1750-1758.
33. Huang YH, Bergles DE. Glutamate transporters bring competition to the synapse [J]. Curr Opin Neurobiol,2004,14:346-352.
34. Zhu Z, Zhang Q, Yu Z, et al. Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo [J]. Glia,2007,55:546-558.
35. Takayama Y, Tanaka S, Nagai K, et al. Adenovirus-mediated overexpression of C-terminal Src kinase (Csk) in type Ⅰ astrocytes interferes with cell spreading and attachment to fibronectin. Correlation with tyrosine phosphorylations of paxillin and FAK [J]. J Biol Chem,1999,274:2291-2297.
36. Jing R, Pizzolato G, Robson RM, et al. Intermediate filament protein synemin is present in human reactive and malignant astrocytes and associates with ruffled membranes in astrocytoma cells [J]. Glia, 2005,50:107-120.
37. Lepekhin EA, Eliasson C, Berthold CH, et al. Intermediate filaments regulate astrocyte motility [J]. J Neurochem,2001,79:617-625.
38. Takemura M, Gomi H, Colucci-Guyon E, et al. Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice [J]. J Neurosci,2002,22:6972-6979.
39. Neary JT, Baker L, Jorgensen SL, et al. Extracellular ATP induces stellation and increases glial fibrillary acidic protein content and DNA synthesis in primary astrocyte cultures [J]. Acta Neuropathol,1994,87:8-13.
40. Nicchia GP, Rossi A, Mola MG, et al. Actin cytoskeleton remodeling governs aquaporin-4 localization in astrocytes [J]. Glia,2008,56:1755-1766.
41. Ren QG, Yu Y, Pan DJ, et al. Lactacystin Stimulates Stellation of Cultured Rat Cortical Astrocytes [J]. Neurochem Res,2009,34:859-866.
42. Wang LP, Cheung G, Kronenberg G, et al. Mild brain ischemia induces unique physiological properties in striatal astrocytes [J]. Glia,2008,59:925-934.
43. Cataldo AM, Broadwell RD. Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. Ⅱ. Choroid plexus and ependymal epithelia, endothelia and pericytes [J]. J Neurocytol,1986,15:511-524.
44. Pellegri G, Rossier C, Magistretti PJ, et al. Cloning, localization and induction of mouse brain glycogen synthase [J]. Brain Res Mol Brain Res,1996,38:191-199.
45. Pfeiffer-Guglielmi B, Fleckenstein B, Jung G, et al. Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies [J]. J Neurochem, 2003,85:73-81.
46. Jaeschke H, Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury [J]. Gastroenterology,2003,125:1246-1257.
47. Xue DB, Zhang WH, Yun XG, et al. Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats [J]. Chin Med J,2007,120:690-695.
1. Chance, B., Sies, H. and Boveris, A. Hydroperoxide metabolism in mammalian organs. Physiological Reviews.1979; 59:527-605
2. 2 Palmer, R.M.J., Rees, D.D., Ashton, D.S. and Moncada, S. L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium dependent relaxation. Biochemical and Biophysical Research Communications.1988;153:1251-1256
3. 4 Gutteridge, J.M. and Halliwell, B. Free radicals and antioxidants in the year 2000. A historical look to the future. Annals of the New York Academy of Science.2000; 899:136-147
4. Goodall, E.F. and Morrison, K.E. Amyotrophic lateral sclerosis (motor neuron disease):proposed mechanisms and pathways to treatment. Expert Reviews in Molecular Medicine.2006; 8:1-22
5. Halliwell, B. Oxidative stress and neurodegeneration:where are we now? Journal of Neurochemistry. 2006; 97:1634-1658
6. Lin, M.T. and Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature.2006; 443:787-795
7. Browne, S.E. and Beal, M.F. Oxidative damage in Huntington's disease pathogenesis. Antioxidants and Redox Signalling.2006; 8:2061-2073
8. Moi, P., Chan, K., Asunis, I. et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proceedings of the National Academy of Sciences of the United States of America.1994; 91:9926-9930
9. Rushmore, T.H. and Pickett, C.B. Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. Journal of Biological Chemistry.1990; 265:14648-14653
10. Andrews, N.C., Erdjument-Bromage, H., Davidson, M.B. et al. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein Nature.1993; 362:722-728
11. Itoh, K., Chiba, T., Takahashi, S. et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and Biophysical Research Communications.1997; 236:313-322
12. Wakabayashi, N., Itoh, K., Wakabayashi, J. et al. Keapl-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nature Genetics.2003; 35:238-245
13. Stewart, D., Killeen, E., Naquin, R. et al. Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium. Journal of Biological Chemistry.2003; 278:2396-2402
14. McMahon, M., Thomas, N., Itoh, K. et al. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism:a two-site interaction model
for the Nrf2-Keapl complex. Journal of Biological Chemistry.2006; 281:24756-24768
15. Dinkova-Kostova, A.T., Holtzclaw, W.D., Cole, R.N. et al. Direct evidence that sulfhydryl groups of Keapl are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proceedings of the National Academy of Sciences of the United States of America.2002; 99: 11908-11913
16. Zhang, D.D. and Hannink, M. Distinct cysteine residues in Keapl are required for Keapl-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Molecular and Cellular Biology.2003; 23:8137-8151
17. Kobayashi, M. and Yamamoto, M. Nrf2-Keapl regulation of cellular defense Mechanismsagainstelectrophilesandreactiveoxygen species. Advances in Enzyme Regulation.2006; 46:113-140
18. Vargas, M.R., Pehar, M., Cassina, P. et al. Fibroblast growth factor-1 induces heme oxygenase-1 via nuclear factor erythroid 2-related factor 2 (Nrf2) in spinal cord astrocytes:consequences for motor neuron survival. Journal of Biological Chemistry.2005; 280:25571-25579
19. Tenhunen, R., Marver, H.S. and Schmid, R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America.1968; 61:748-755
20. Maines, M.D. Heme oxygenase:function, multiplicity, regulatory mechanisms, and clinical applications. The FASEB Journal.1988; 2:2557-2568
21. Shibahara, S.,Mu" ller,R., Taguchi,H. andYoshida, T. Cloningandexpressionof cDNAfor rat heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America.1985; 82:7865-7869
22. Maines, M.D., Trakshel, G.M. and Kutty, R.K. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. Journal of Biological Chemistry.1986; 261:411-419
23. Baranano, D. E. and Snyder, S.H. Neural roles for heme oxygenase:contrasts to nitric oxide synthase. Proceedings of the National Academy of Sciences of the United States of America.2001; 98: 10996-11002
24. Dwyer, B.E., Nishimura, R.N. and Lu, S.Y. Differential expression of heme oxygenase-1 in cultured cortical neurons and astrocytes determined by the aid of a new heme oxygenase antibody. Response to oxidative stress. Brain Research Molecular Brain Research.1995; 30:37-47
25. Stocker, R., Yamamoto, Y., McDonagh, A.F. et al. Bilirubin is an antioxidant of possible physiological importance. Science.1987; 235:1043-1046
26. Ferris, C.D., Jaffrey, S.R., Sawa, A. et al. Haem oxygenase-1 prevents cell death by regulating cellular iron. Nature Cell Biology.1999; 1:152-157
27. Schipper, H.M. Brain iron deposition and the free radical-mitochondrial theory of ageing. Ageing Research Reviews.2004; 3:265-301
28. Ferrante, R.J., Shinobu, L.A., Schulz, J.B. et al. Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Annals of Neurology.1997; 42: 326-334
29. Ho, Y.S., Magnenat, J.L., Bronson, R.T. et al. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. Journal of Biological Chemistry. 1997; 272:16644-16651
30. Dringen, R., Pawlowski, P.G. and Hirrlinger, J. Peroxide detoxification by brain cells. Journal of Neuroscience Research.2005; 79:157-165
31. Cole, S.P. and Deeley, R.G. Transport of glutathione and glutathione conjugates by MRP1. Trends in Pharmacological Sciences.2006; 27:438-446
32. Meister, A. Glutathione metabolism and its selective modification. Journal of Biological Chemistry. 1988;263:17205-17208
33. Moinova, H.R. and Mulcahy, R.T. Up-regulation of the human gammaglutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element. Biochemical and Biophysical Research Communications.1999; 261:661-668
34. Sasaki, H., Sato, H., Kuriyama-Matsumura, K. et al. Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. Journal of Biological Chemistry.2002; 277:44765-44771
35. Thimmulappa, R.K., Lee, H., Rangasamy, T. et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. Journal of Clinical Investigation.2006; 116:
984-995
36. Suh, J.H., Shenvi, S.V., Dixon, B.M. et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proceedings of the National Academy of Sciences of the United States of America.2004;101:3381-3386
37. Morito, N., Yoh, K., Itoh, K. et al. Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels. Oncogene.2003; 22:9275-9281
38. Pehar, M., Vargas, M.R., Robinson, K.M. et al. Mitochondrial superoxide production and nuclear factor erythroid 2-related factor 2 activation in p75 neurotrophin receptor-induced motor neuron apoptosis. Journal of Neuroscience.2007; 27:7777-7785
39. Drukarch, B., Schepens, E., Jongenelen, C.A. et al. Astrocyte-mediated enhancement of neuronal survival is abolished by glutathione deficiency. Brain Research.1997; 770:123-130
40. Sagara, J., Miura, K. and Bannai, S. Cystine uptake and glutathione level in fetal brain cells in primary culture and in suspension. Journal of Neurochemistry.1993; 61:1667-1671
41. Lee, J.M., Calkins, M.J., Chan, K. et al. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. Journal of Biological Chemistry.2003; 278:12029-12038
42. Shih, A.Y., Johnson, D.A., Wong, G., Kraft, A.D., Jiang, L., Erb, H., Johnson, J.A. and Murphy, T.H. Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. Journal of Neuroscience.2003; 23:3394-3406
43. Guo, N. and Shaw, C. Characterization and localization of glutathione binding sites on cultured astrocytes. Brain Research Molecular Brain Research.1992; 15:207-215
44. Dringen, R., Pfeiffer, B. and Hamprecht, B. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. Journal of Neuroscience.1999; 19:562-569
45. Hirrlinger, J., Ko"nig, J., Keppler, D. et al. The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress. Journal of Neurochemistry. 2001;76:627-636
46. Dringen, R., Kranich, O. and Hamprecht, B. The gamma-glutamyl transpeptidase inhibitor acivicin preserves glutathione released by astroglial cells in culture. Neurochemical Research.1997; 22:
727-733
47. Van Muiswinkel, F.L. and Kuiperij, H.B. The Nrf2-ARE Signalling pathway:promising drug target to combat oxidative stress in neurodegenerative disorders. Current Drug TargetsCNSand Neurological Disorders.2005; 4:267-281
48. Lewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma.2000; 17:871-90.
49. Kontos HA.Oxygen radicals in cerebral ischemia:the 2001 Willis lecture. Stroke.2001; 32:2712-6.
50. Althaus JS, Andrus PK, Williams CM, VonVoigtlander PF, Cazers AR, Hall ED. The use of salicylate hydroxylation to detect hydroxyl radical generation in ischemic and traumatic brain injury. Reversal by tirilazad mesylate (U-74006F). Mol Chem Neuropathol.1993; 20:147-62.
51. Bates B, Hirt L, Thomas SS, Akbarian S, Le D, Amin-Hanjani S, Whalen M, Jaenisch R, Moskowitz MA. Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress:possible involvement of oxygen free radicals. Neurobiol Dis.2002; 9:24-37.
52. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab.2001; 21:2-14.
53. Shah ZA, Li RC, Thimmulappa RK, Kensler TW, Yamamoto M, Biswal S, Dore S. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience.2007;147: 53-59.
54. Shih AY, Li P, Murphy TH. A small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo. J Neurosci.2005; 25:10321-10335.
55. Danilov CA, Chandrasekaran K, Racz J, et al. Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation. Glia.2009; 57(6):645-56.
56. Rosen, D.R., Siddique, T., Patterson, D. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature.1993; 362:59-62
57. Manfredi, G. and Xu, Z. Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. Mitochondrion.2005; 5:77-87
58. Boille'e, S., Yamanaka, K., Lobsiger, C.S. et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science.2006; 312:1389-1392
59. Este'vez, A.G., Spear, N., Manuel, S.M. et al. Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. Journal of Neuroscience.1998;18:923-931
60.134 Sarlette, A., Krampfl, K., Grothe, C. et al. Nuclear erythroid 2-related factor 2-antioxidative response element signaling pathway in motor cortex and spinal cord in amyotrophic lateral sclerosis. Journal of Neuropathology and Experimental Neurology.2008; 67:1055-1062
61. Ferraiuolo, L., Heath, P.R., Holden, H. et al. Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. Journal of Neuroscience.2007; 27:9201-9219
62. Nagai, M., Re, D.B., Nagata, T. et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nature Neuroscience.2007; 10:615-622
63. Thomas, B. and Beal, M.F. Parkinson's disease. Human Molecular Genetics.2007; 16:R183-R194
64. Alam, Z.I., Daniel, S.E., Lees, A.J. et al. A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. Journal of Neurochemistry.1997; 69:1326-1329
65. Schipper, H.M. Heme oxygenase expression in human central nervous system disorders. Free Radical Biology and Medicine.2004; 37:1995-2011
66. Wruck, CJ, Claussen, M., Fuhrmann, G. et al. Luteolin protects rat PC 12 and C6 cells against MPPt induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway. Journal of Neural Transmission Suppl.2007; 72:57-67
67. Burton, N.C., Kensler, T.W. and Guilarte, T.R. In vivo modulation of the Parkinsonian phenotype by Nrf2. Neurotoxicology.2006; 27,1094-1100
68. Chen, P.C., Vargas, M.R., Pani, A.K. et al. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease:a critical role for the astrocyte. Proceedings of the National Academy of Sciences of the United States of America.2009; 106:2933-2938
1. Nonaka T, Kuwae A, Sasakawa C, Imajoh-Ohmi S. Shigella flexneri YSH6000 induces two types of cell death, apoptosis and oncosis, in the differentiated human monoblastic cell line U937. [J].FEMS Microbiol Lett.1999 May 1,174(1):89-95.
2. Majno G, Joris I.Apoptosis, oncosis, and necrosis:an overview of cell death. [J].Am J Pathol,1995, 146:3-15.
3. Levin S. Apoptosis, necrosis, or oncosis:what is your diagnosis? a report from the Cell Death Nomenclature Committee of the Society of Toxicologic Pathologists.[J]. Toxicol. Sci.1998 41: 155-156.
4. Estacion M, Schilling WP. Blockade of maitotoxin-induced oncotic cell death reveals zeiosis. [J].BMC Physiol 2002; 2:2.
5. Dacheux D,Toussaint B, Richard M, Brochier G, Croize J, Attree I. Pseudomonas aeruginosa cystic fibrosis isolates induce rapid, type Ⅲ secretion-dependent, oncosis of macrophages and polymorphonuclear neutrophils. [J]. Infect Immun,2000,68:2916-2924.
6. Elsasser A, Suzuki K, and Schaper J. Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. [J]. Mol Cell Cardiol.2000.32:711-724.
7. Ohno M, Takemura G, Misao J, Hayakawa Y, Minatoguchi S, Fujiwara T. "Apoptotic" myocytes in infarct area in rabbit hearts may be oncotic myocytes with DNA fragmentation:analysis by immunogold electron microscopy combined with In situ nick end-labeling [J].Circulation 1998; 98:. 1422-1430.
8. D.R.Hunter, R.A.Haworth. The Ca2+-induced membrane transition in mitochondria Ⅲ. Transitional Ca2+release. [J].Arch Biochem Biophys.1979 Jul,195(2):468-477.
9. G, Reed JC. Mitochondrial control of cell death. [J].Nat Med.2000,6:513-519.
10. P. Bernardi, A. Krauskopf, E. Basso, V. Petronilli, E. Blachy-Dyson, F. Di Lisa, M. Forte, The mitochondrial permeability transition from in vitro artifacts to disease target. [J]. FEBS.2006.273: 2077-2099.
11. Kass GE, Orrenius S.Calcium signaling and cytotoxicity. [J].Environ. Health. Perspect.1999; 107:25-35.
12. Lemasters JJ, Qian T, He L, J.S. Kim, S.P. Elmore, W.E. Cascio, D.A. Brenner. Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. [J]. Antioxid Redox Signal 2002;4:769-781.
13.李树清,罗海芸.缺血后适应对树鼬海马CA1区脑血流及星形胶质细胞活化的影响及可能机制.[J].中国病理生理杂志,2008,24(6)：1090-1095.
14. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. [J]. Am J Physiol Renal Physiol,1998,274:F315-F327.
15. Mills EM, Xu D, Fergusson MM, Combs CA, Xu Y and Finkel T. Regulation of Cellular Oncosis by Uncoupling Protein 2. [J]. Biol Chem.2002,277:27385-27392.
16. Oberkofler H, Iglseder B, Klein K, Unger J, Haltmayer M. associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women. [J]. Arterioscler Thromb Vasc Biol 2005, 25:604-610.
17. Holler N, Zaru R, Micheau 0, Thome M, Thome A, Attinger, S Valitutti, J.L. Bodmer, P. Schneider, B. Seed, J. Tschopp. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. [J].Nat Immunology,2000,1(6):489-495.
18. Y. Lin, S. Choksi, H.-M. Shen, Q. F. Yang, G. M. Hur, Y. S. Kim, J. H. Tran, S. A. Nedospasov, and Z.-g. Liu. Tumor necrosis factorinduced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. [J].Biol. Chem.2004,279: 10822-10828.
19. Ma F, Zhang C, Prasad KV, et al. Molecular cloning of porimin, a novel cell surface receptor mediating oncotic cell death. [J]. Proc Natl Acad Sci USA,2001,98(17):9778-9783.
20. Barros LF, Stutzin A, Calixto A, et al. Nonselective cation channels as effectors of free radical-induced rat liver cell necrosis [J]. Hepatology,2001,33 (1):114-122.
21. Cummings BS, McHowat J, Schnellmann RG. Phospholipase A (2) s in cell injury and death. [J]. J Pharmacol Exp Ther,2000,294(3):793-799.
22. Harriman JF, Liu XL, Aleo MD, et al. Endoplasmic reticulum Ca2+signaling and calpains mediate renal cell death. [J].Cell Death Differ,2002,9:734-741.
23. Krysko O, de Ridder L, and Cornelissen M. Phosphatidylserine exposure during early primary necrosis (oncosis) in JB6 cells as evidenced by immunogold labelling technique. [J]. Apoptosis 2004, 9:495-500.
24. Croall DE, DeMartino GN. Calcium-activated neutral protease (calpain) system:structure, function and regulation. [J]. Physiol Rev,1991,71(3):813-847.
25. Kern JC, Kehrer JP. Acrolein-induced cell death:a caspase-influenced decision between apoptosis and oncosisPnecrosis. [J]. Chem Biol Interact,2002,139 (1):79-95.
26. Chang SH, Phelp s PC, Berezesky IK, et al. Studies on the mechanisms and kinetics of apop tosis induced by microinjection of cytochrome c in rat kidney tubule ep ithelial cells (NRK-52E). [J]. Am J Pathol,2000,156 (2):637-649.
27. Los M, Mozoluk M, Ferrari D, et al. Activation and caspase-mediate inhibition of PARP:amolecular swithch between fibroblast necrosis and apop tosis in death recep torsignaling. [J]. Mol Biol Cell, 2002,13:978-988.
28. Bovia F, Nabili-Tehrani AC, Werner-Favre C, Barnet M, Kindler V, Zubler RH (1998) Quiescent memory B cells in human peripheral blood co-express bcl-2 and bcl-x(L) anti-apoptotic proteins at high levels. Eur J Immunol.28:4418-4423.
29. Gujral JS, Farhood A, Jaeschke H. Oncotic necrosis and caspase-dependent apoptosis during galactosamine-induced liver injury in rats. [J]. Toxicol Appl Pharmacol,2003,190 (1):37-46.
30. Ryoke T, Gu Y, Ikeda Y, et al. Apop tosis and oncosis in the early p rogression of left ventricular dysfunction in the cardiomyopathic hamster [J]. Basic Res Cardiol,2002,97 (1):65-75.
31. Rabkin SW, Kong JY. Lovastatin-induced cardiac toxicity involves both oncotic and apop totic cell death with the apoptotic component blunted by both caspase-2 and caspase-3 inhibitors [J]. Toxicol App 1 Pharmacol,2003,193 (3):346-355.
32. Willems L, Zatta A, Holmgren K, et al. Age-related changes in ischemic tolerance in male and female mouse hearts. [J]. Mol Cell Cardiol,2005,38 (2):245-256.
33. Fickert P, TraunerM, Fuchsbichler A, et al. Oncosis represents the main type of cell death in mouse models of cholestasis. [J]. Hepatol,2005,42 (3):378-385.
© 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 |