DAP5 Ameliorates Cisplatin-Induced Apoptosis of Renal Tubular Cells
DAP5 Ameliorates Cisplatin-Induced Apoptosis of Renal Tubular Cells
复制标题
DAP5 改善顺铂诱导的肾小管细胞凋亡
DOI：
10.1159/000338302
复制
发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Chen, Xiang-mei
中科院分区：
文献类型：
--
作者：
Gao, Jian-jun;Cai, Guang-yan;Chen, Xiang-mei
背景：顺铂的肾毒性限制了其临床应用。顺铂诱导急性肾小管上皮细胞凋亡是顺铂肾毒性的主要机制之一。本研究探讨死亡相关蛋白5（DAP 5）在顺铂诱导肾小管细胞凋亡中的作用及其调控。研究方法：在人肾小管上皮细胞系（HKC）中通过质粒转染上调DAP 5表达和通过小干扰RNA下调DAP 5表达后，通过流式细胞术分析评估细胞凋亡的程度。Western blot检测Bax和Bcl-2蛋白表达。还评估了PI 3 K/Akt/mTOR信号通路与DAP 5之间的关系。结果：在顺铂诱导的HKC细胞凋亡过程中，DAP 5发生蛋白水解断裂，产生86 kDa的物种，DAP 5/p86。DAP 5/p97和DAP 5/p86的过表达增加了Bcl-2的翻译，降低了顺铂诱导的细胞凋亡的程度。使用小干扰RNA敲低DAP 5表达降低了Bcl-2的翻译，并增加了凋亡的程度。两种处理均不影响Bax的表达。DAP 5的表达受PI 3 K/Akt/mTOR信号通路的正调控。结论：总的来说，本研究的结果揭示了DAP 5在顺铂诱导的细胞凋亡中的新作用：DAP 5/p97和DAP 5/p86增强抗凋亡蛋白Bcl-2的翻译并抑制顺铂诱导的细胞凋亡。PI 3 K/Akt/mTOR信号通路可能正调控DAP 5的表达。版权所有（C）2012 S. Karger AG，巴塞尔
Background: Nephrotoxicity of cisplatin limits its clinical application. Cisplatin-induced acute renal tubular epithelial cell apoptosis is one of the major mechanisms of cisplatin nephrotoxicity. Here, the role and regulation of death-associated protein 5 (DAP5) in cisplatin-induced tubular cell apoptosis were investigated. Methods: After upregulation of DAP5 expression by plasmid transfection and downregulation of DAP5 expression by small interfering RNA in human kidney tubular epithelial cell line (HKC) cells, the degree of cell apoptosis was assessed by flow cytometric analysis. The expression of Bax and Bcl-2 proteins was detected by Western blot analysis. The relationship between the PI3K/Akt/mTOR signaling pathway and DAP5 was also evaluated. Results: During cisplatin-induced apoptosis in HKC cells, DAP5 underwent proteolytic fragmentation, yielding an 86-kDa species, DAP5/p86. Overexpression of DAP5/p97 and DAP5/p86 increased the translation of Bcl-2 and reduced the extent of cisplatin-induced apoptosis. Knockdown of DAP5 expression using small interfering RNA decreased the translation of Bcl-2 and increased the degree of apoptosis. Neither manipulation affected the expression of Bax. DAP5 expression was positively regulated by the PI3K/Akt/mTOR signaling pathway. Conclusion: Collectively, the results from the present study revealed a new role for DAP5 in cisplatin-induced apoptosis: DAP5/p97 and DAP5/p86 enhanced the translation of the anti-apoptotic protein Bcl-2 and inhibited cisplatin-induced apoptosis. The PI3K/Akt/mTOR signaling pathway may positively regulate the expression of DAP5. Copyright (C) 2012 S. Karger AG, Basel