Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress.
Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress.
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DOI：
10.1159/000320593
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Bin Sun;Chao Lu;Guo-Ping Zhou;C. Xing
中科院分区：
文献类型：
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作者：
Bin Sun;Chao Lu;Guo-Ping Zhou;C. Xing
背景氧化应激是细胞凋亡的重要诱导因子，在肾脏炎症的发生发展中起关键作用。前列腺凋亡反应因子-4 （Par-4）基因最初是在发生凋亡的前列腺细胞中发现的。随后，par4被发现在各种细胞系统中具有强大的促凋亡活性。然而，par4是否参与肾小管上皮细胞的氧化损伤尚不清楚。目的探讨Par-4在氧化应激诱导肾近端小管细胞凋亡中的作用。方法用小干扰RNA沉默par4基因的表达。将肾近端小管细胞暴露于过氧化氢中，观察Par-4沉默对细胞凋亡、磷酸化Akt和血管内皮生长因子表达的影响。结果过氧化氢诱导人肾近端小管上皮细胞凋亡并增加Par-4表达。par4沉默通过激活PI3K/Akt信号通路，在Akt磷酸化增强的情况下显著保护肾近端小管细胞免于凋亡。par4沉默还可以改善氧化应激诱导的血管内皮生长因子表达下调。结论par4基因沉默导致PI3K/Akt信号依赖性抑制氧化应激后肾近端小管细胞凋亡。
BACKGROUND Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells. AIMS To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress. METHODS Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined. RESULTS Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress. CONCLUSION Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.