Division of Nephrology, Department of Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Nephron Exp Nephrol. 2011;117(3):e53-61. doi: 10.1159/000320594.
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.
To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress.
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.
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.
Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.
氧化应激是细胞凋亡的重要诱导因素，在肾脏炎症的发展中起着关键作用。前列腺细胞凋亡反应因子-4（Par-4）基因最初在发生凋亡的前列腺细胞中被鉴定出来。随后，发现 Par-4 在各种细胞系统中具有很强的促凋亡活性。然而，目前尚不清楚 Par-4 是否参与了肾小管上皮细胞的氧化应激损伤。
确定 Par-4 在氧化应激诱导的肾近端管状细胞凋亡中的作用。
通过小干扰 RNA 沉默 Par-4 基因表达。然后将肾近端管状细胞暴露于过氧化氢中，并测定 Par-4 沉默对细胞凋亡以及磷酸化 Akt 和血管内皮生长因子表达的影响。
过氧化氢诱导人肾近端管状上皮细胞凋亡并增加 Par-4 表达。Par-4 沉默通过激活 PI3K/Akt 信号通路显著保护肾近端管状细胞免于凋亡，因为 Akt 磷酸化增强。Par-4 沉默还改善了氧化应激诱导的血管内皮生长因子表达下调。
Par-4 基因沉默导致 PI3K/Akt 信号依赖性抑制氧化应激后肾近端管状细胞凋亡。
