凋亡相关蛋白、信号通路在肾小管上皮细胞凋亡中的作用机制研究进展
摘要
凋亡是细胞在内外微环境改变时,以半胱氨酸蛋白酶(caspase)激活为主要特征,多种途径、多个细胞器共同参与的一种调控性细胞死亡。凋亡可分为内源性凋亡和外源性凋亡。肾小管上皮细胞凋亡相关的主要蛋白有Bcl-2蛋白家族、死亡受体、caspase。Bcl-2蛋白家族主要参与肾小管上皮细胞内源性凋亡,死亡受体主要参与肾小管上皮细胞外源性凋亡,caspase激活是肾小管上皮细胞凋亡的核心机制。丝裂原活化蛋白激酶(MAPK)、酪氨酸激酶(JAK)-转导和转录激活因子(STAT)、3-磷酸肌醇激酶(PI3K)-丝氨酸/苏氨酸激酶(Akt)等多种信号通路也参与肾小管上皮细胞凋亡。MAPK信号通路广泛参与肾脏缺血再灌注损伤导致的肾小管上皮细胞凋亡; JAKSTAT信号通路中与肾小管上皮细胞凋亡最相关的是JAK2和STAT3; PI3K-Akt信号通路可发挥抗凋亡作用。
引文
[1] Kerr JF,Wyllie AH,Currie AR. Apoptosis:a basic biological phenomenon with wideranging implications in tissue kinetics[J].Br J Cancer,1972,26(4):239-257.
[2]Galluzzi L,Vitale I,Aaronson SA,et al. Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018[J]. Cell Death Differ,2018,25(3):486-541.
[3]Tsogbadrakh B,Ryu H,Ju KD,et al. AICAR,an AMPK activator,protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway[J]. Biochem Biophys Res Commun,2019,509(3):680-686.
[4]Zhang XQ,Dong JJ,Cai T,et al. High glucose induces apoptosis via upregulation of Bim expression in proximal tubule epithelial cells[J]. Oncotarget,2017,8(15):24119-24129.
[5]Yang Y,Wang X,Zhang Y,et al. Hepatitis B virus X protein and proinflammatory cytokines synergize to enhance TRAIL-induced apoptosis of renal tubular cells by upregulation of DR4[J]. Int J Biochem Cell Biol,2018,97:62-72.
[6]Arnoult D,Gaume B,Karbowski M,et al. Mitochondrial release of AIF and EndoG requirescaspase activation downstream of Bax/Bak‐mediated permeabilization[J]. EMBOJ,2003,22(17):4385-4399.
[7]Girnius N,Davis RJ. JNK Promotes epithelial cell anoikis by transcriptional and post-translational regulation of BH3-only proteins[J]. Cell Rep,2017,21(7):1910-1921.
[8]Pfeffer CM,Singh ATK. Apoptosis:a target for anticancer therapy[J]. Int J Mol Sci,2018,19(2):448.
[9] Galluzzi L,Bravo-San Pedro JM,Kroemer G. Organelle-specific initiation of cell death[J]. Nat Cell Biol,2014,16(8):728-736.
[10]Song H,Han IY,Kim Y,et al. The NADPH oxidase inhibitor DPI can abolish hypoxia-induced apoptosis of human kidney proximal tubular epithelial cells through Bcl-2 up-regulation via ERK activation without ROS reduction[J]. Life Sci,2015,126:69-75.
[11] He P,Zhou G,Qu D,et al. HBx inhibits proliferation and induces apoptosis via Fas/Fas L upregulation in rat renal tubular epithelial cells[J]. J Nephrol,2013,26(6):1033-1041.
[12]Chen H,Huang RS,Yu XX,et al. Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation[J]. Exp Ther Med,2017,14(1):447-452.
[13]Hosny G,Ismail W,Makboul R,et al. Increased glomerular Bax/Bcl-2 ratio is positively correlated with glomerular sclerosis in lupus nephritis[J]. Pathophysiology,2018,25(2):83-88.
[14]Schleich K,Buchbinder JH,Pietkiewicz S,et al. Molecular architecture of the DED chains at the DISC:regulation of procaspase-8activation by short DED proteins c-FLIP and procaspase-8 prodomain[J]. Cell Death Differ,2016,23(4):681-694.
[15] Wang Y,Mu Y,Zhou X,et al. SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering Fas L-induced cell apoptosis during renal ischemia reperfusion[J]. Apoptosis,2017,22(4):519-530.
[16]Lu Y,Yuan H,Deng S,et al. Arsanilic acid causes apoptosis and oxidative stress in rat kidney epithelial cells(NRK-52e cells)by the activation of thecaspase-9 and-3 signaling pathway[J]. Drug Chem Toxicol,2014,37(1):55-62.
[17]Heutinck KM,Rowshani AT,Kassies J,et al. Viral double-stranded RNA sensors induce antiviral,pro-inflammatory,and pro-apoptotic responses in human renal tubular epithelial cells[J]. Kidney Int,2012,82(6):664-675.
[18]Chung H,Vilaysane A,Lau A,et al. NLRP3 regulates a non-canonical platform forcaspase-8 activation during epithelial cell apoptosis[J]. Cell Death Differ,2016,23(8):1331-1346.
[19]Zhang B,Rong R,Li H,et al. Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury[J]. Mol Med Rep,2015,11(3):1793-1799.
[20]Chen J,Wang W,Zhang Q,et al. Low Molecular weight fucoidan against renal ischemia-reperfusion Injury via Inhibition of the MAPK signaling pathway[J]. PLo S One,2013,8(2):e56224.
[21]Choi DE,Jeong JY,Choi H,et al. ERK phosphorylation plays an important role in the protection afforded by hypothermia against renal ischemia-reperfusion injury[J]. Surgery,2017,161(2):444-452.
[22] Wu H,Shi Y,Deng X,et al. Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice[J]. Mol Cell Endocrinol,2015,417:27-35.
[23] Tian Y,Han YX,Guo HF,et al. Upregulated microRNA-485suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF-β-MAPK signaling pathway by inhibiting RhoA expression[J]. J Cell Biochem,2018,119(11):9154-9167.
[24]He P,Zhang D,Li H,et al. Hepatitis B virus X protein modulates apoptosis in human renal proximal tubular epithelial cells by activating the JAK2/STAT3 signaling pathway[J]. Int J Mol Med,2013,31(5):1017-1029.
[25]Erkasap S,Erkasap N,Bradford B,et al. The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats[J]. Bratisl Lek Listy,2017,118(8):443-448.
[26]Xu MJ,Feng D,Wang H,et al. IL-22 ameliorates renal ischemiareperfusion injury by targeting proximal tubule epithelium[J]. J Am Soc Nephrol,2014,25(5):967-977.
[27]Long Q,Li X,He H,et al. Autophagy activation protects shock wave induced renal tubular epithelial cell apoptosis may through modulation of Akt/GSK-3βpathway[J]. Int J Biol Sci,2016,12(12):1461-1471.
[2]Galluzzi L,Vitale I,Aaronson SA,et al. Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018[J]. Cell Death Differ,2018,25(3):486-541.
[3]Tsogbadrakh B,Ryu H,Ju KD,et al. AICAR,an AMPK activator,protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway[J]. Biochem Biophys Res Commun,2019,509(3):680-686.
[4]Zhang XQ,Dong JJ,Cai T,et al. High glucose induces apoptosis via upregulation of Bim expression in proximal tubule epithelial cells[J]. Oncotarget,2017,8(15):24119-24129.
[5]Yang Y,Wang X,Zhang Y,et al. Hepatitis B virus X protein and proinflammatory cytokines synergize to enhance TRAIL-induced apoptosis of renal tubular cells by upregulation of DR4[J]. Int J Biochem Cell Biol,2018,97:62-72.
[6]Arnoult D,Gaume B,Karbowski M,et al. Mitochondrial release of AIF and EndoG requirescaspase activation downstream of Bax/Bak‐mediated permeabilization[J]. EMBOJ,2003,22(17):4385-4399.
[7]Girnius N,Davis RJ. JNK Promotes epithelial cell anoikis by transcriptional and post-translational regulation of BH3-only proteins[J]. Cell Rep,2017,21(7):1910-1921.
[8]Pfeffer CM,Singh ATK. Apoptosis:a target for anticancer therapy[J]. Int J Mol Sci,2018,19(2):448.
[9] Galluzzi L,Bravo-San Pedro JM,Kroemer G. Organelle-specific initiation of cell death[J]. Nat Cell Biol,2014,16(8):728-736.
[10]Song H,Han IY,Kim Y,et al. The NADPH oxidase inhibitor DPI can abolish hypoxia-induced apoptosis of human kidney proximal tubular epithelial cells through Bcl-2 up-regulation via ERK activation without ROS reduction[J]. Life Sci,2015,126:69-75.
[11] He P,Zhou G,Qu D,et al. HBx inhibits proliferation and induces apoptosis via Fas/Fas L upregulation in rat renal tubular epithelial cells[J]. J Nephrol,2013,26(6):1033-1041.
[12]Chen H,Huang RS,Yu XX,et al. Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation[J]. Exp Ther Med,2017,14(1):447-452.
[13]Hosny G,Ismail W,Makboul R,et al. Increased glomerular Bax/Bcl-2 ratio is positively correlated with glomerular sclerosis in lupus nephritis[J]. Pathophysiology,2018,25(2):83-88.
[14]Schleich K,Buchbinder JH,Pietkiewicz S,et al. Molecular architecture of the DED chains at the DISC:regulation of procaspase-8activation by short DED proteins c-FLIP and procaspase-8 prodomain[J]. Cell Death Differ,2016,23(4):681-694.
[15] Wang Y,Mu Y,Zhou X,et al. SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering Fas L-induced cell apoptosis during renal ischemia reperfusion[J]. Apoptosis,2017,22(4):519-530.
[16]Lu Y,Yuan H,Deng S,et al. Arsanilic acid causes apoptosis and oxidative stress in rat kidney epithelial cells(NRK-52e cells)by the activation of thecaspase-9 and-3 signaling pathway[J]. Drug Chem Toxicol,2014,37(1):55-62.
[17]Heutinck KM,Rowshani AT,Kassies J,et al. Viral double-stranded RNA sensors induce antiviral,pro-inflammatory,and pro-apoptotic responses in human renal tubular epithelial cells[J]. Kidney Int,2012,82(6):664-675.
[18]Chung H,Vilaysane A,Lau A,et al. NLRP3 regulates a non-canonical platform forcaspase-8 activation during epithelial cell apoptosis[J]. Cell Death Differ,2016,23(8):1331-1346.
[19]Zhang B,Rong R,Li H,et al. Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury[J]. Mol Med Rep,2015,11(3):1793-1799.
[20]Chen J,Wang W,Zhang Q,et al. Low Molecular weight fucoidan against renal ischemia-reperfusion Injury via Inhibition of the MAPK signaling pathway[J]. PLo S One,2013,8(2):e56224.
[21]Choi DE,Jeong JY,Choi H,et al. ERK phosphorylation plays an important role in the protection afforded by hypothermia against renal ischemia-reperfusion injury[J]. Surgery,2017,161(2):444-452.
[22] Wu H,Shi Y,Deng X,et al. Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice[J]. Mol Cell Endocrinol,2015,417:27-35.
[23] Tian Y,Han YX,Guo HF,et al. Upregulated microRNA-485suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF-β-MAPK signaling pathway by inhibiting RhoA expression[J]. J Cell Biochem,2018,119(11):9154-9167.
[24]He P,Zhang D,Li H,et al. Hepatitis B virus X protein modulates apoptosis in human renal proximal tubular epithelial cells by activating the JAK2/STAT3 signaling pathway[J]. Int J Mol Med,2013,31(5):1017-1029.
[25]Erkasap S,Erkasap N,Bradford B,et al. The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats[J]. Bratisl Lek Listy,2017,118(8):443-448.
[26]Xu MJ,Feng D,Wang H,et al. IL-22 ameliorates renal ischemiareperfusion injury by targeting proximal tubule epithelium[J]. J Am Soc Nephrol,2014,25(5):967-977.
[27]Long Q,Li X,He H,et al. Autophagy activation protects shock wave induced renal tubular epithelial cell apoptosis may through modulation of Akt/GSK-3βpathway[J]. Int J Biol Sci,2016,12(12):1461-1471.