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c-Myc promotes tubular cell apoptosis in ischemia-reperfusioninduced renal injury by negatively regulating c-FLIP and enhancing FasL/Fas-mediated apoptosis pathway

   
@article{APS10009,
	author = {Dan Xu and Bao Wang and Pan-pan Chen and Yan-zhe Wang and Nai-jun Miao and Fan Yin and Qian Cheng and Zhuan-li Zhou and Hong-yan Xie and Li Zhou and Jun Liu and Xiao-xia Wang and Hong Xue and Wei Zhang and Li-min Lu},
	title = {c-Myc promotes tubular cell apoptosis in ischemia-reperfusioninduced renal injury by negatively regulating c-FLIP and enhancing FasL/Fas-mediated apoptosis pathway},
	journal = {Acta Pharmacologica Sinica},
	volume = {40},
	number = {8},
	year = {2019},
	keywords = {},
	abstract = {c-Myc plays an important role in cell proliferation, differentiation, and cell apoptosis. FasL/Fas pathway is a key regulator of cell apoptosis. This study was aimed to investigate the effects of c-Myc on the FasL/Fas pathway in ischemia-reperfusion (I/R)-induced renal injury. Rats were objected to bilateral renal ischemia for 60 min and reperfused for 24 or 48 h. NRK-52E cells were treated with hypoxia-reoxygenation (H/R) or FasL. Immunohistochemistry was used to identify the distribution of c-Myc. Cell apoptosis was assessed by TUNEL staining. Ad-c-Myc and recombinant pcDAN 3.0 were used to overexpress c-Myc and c-FLIP, respectively. ChIP assay and luciferase assay were used to detect the binding of c-Myc to c-FLIP promoter. In I/R rats, c-Myc was increased significantly and mainly located in renal tubular epithelial cells; meanwhile, c-FLIP was decreased, cleaved caspase-8, cleaved caspase-3 and TUNEL-positive staining cells were increased. Treatment of I/R rats with c-Myc inhibitor 10058-F4 significantly attenuated the decrease in c-FLIP, the increase in cleaved caspase-8, cleaved caspase-3, TUNEL-positive cells, Scr and BUN in I/R rats. In NRK-52E cells, hypoxia and reoxygen induced the increase in c-Myc and decrease in c-FLIP. ChIP and luciferase assay results indicated that c-Myc binds to the promoter region of c-FLIP gene. Overexpression of c-Myc markedly decreased c-FLIP. Overexpression of c-FLIP inhibited the increase in cleaved caspase-8 and caspase-3 induced by FasL. Data indicated that c-Myc is increased in kidneys of I/R rats and negatively regulates the expression of c-FLIP, then enhanced FasL-induced cell apoptosis in I/R stress.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10009}
}