DAP5 ameliorates cisplatin-induced apoptosis of renal tubular cells

American Journal of Nephrology
Jian-jun GaoXiang-mei Chen

Abstract

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. 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. 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 sig...Continue Reading

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Citations

Jun 21, 2012·Biochemical and Biophysical Research Communications·Sham S KakarMiranda Y Fong
Nov 30, 2019·Oxidative Medicine and Cellular Longevity·Wanfen ZhangBicheng Liu
Aug 31, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Congchao JiaRong Chen

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