Inhibition of cadmium-induced apoptosis by glutathione S-transferase P1 via mitogen-activated protein kinases and mitochondrial pathways

Chao Zhang; Xia Yuan; Weiping Mao; Ling Yue; Xiuqin Kong; Yanhong Gao; Lan Luo; Zhimin Yin

doi:10.1016/j.etap.2010.06.004

Inhibition of cadmium-induced apoptosis by glutathione S-transferase P1 via mitogen-activated protein kinases and mitochondrial pathways

Environ Toxicol Pharmacol. 2010 Sep;30(2):202-8. doi: 10.1016/j.etap.2010.06.004. Epub 2010 Jul 21.

Authors

Chao Zhang¹, Xia Yuan, Weiping Mao, Ling Yue, Xiuqin Kong, Yanhong Gao, Lan Luo, Zhimin Yin

Affiliation

¹ Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, PR China.

PMID: 21787653
DOI: 10.1016/j.etap.2010.06.004

Abstract

Cadmium is a well-known toxic metal for the kidney. Glutathione S-transferase P1 (GSTP1) plays an important role in the detoxification and xenobiotics metabolism. Here, we investigated whether GSTP1 affected Cd(2+)-induced apoptotic cell death in human embryonic kidney cell line (HEK) 293 cells. We showed that in HEK293 cells, silencing of GSTP1 expression through RNA interference reinforced the loss in cell viability induced by Cd(2+). Overexpression of GSTP1 inhibited loss of mitochondrial membrane potential, prevented cytochrome c release from mitochondria and caspase-3 activation, inhibited mitogen-activated protein kinases (MAPKs) including ERK, JNK and p38, and suppressed apoptosis induced by Cd(2+). The oligonucleosomal DNA fragmentation assay also demonstrated that overexpression of GSTP1 by adenovirus infection prevented Cd(2+)-induced apoptosis in primary renal tubule cells. Our data suggest that GSTP1 was an endogenous inhibitor of Cd(2+)-induced apoptosis.