title: Inhibition of cadmium-induced apoptosis by glutathione S-transferase P1 via mitogen-activated protein kinases and mitochondrial pathways.
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.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Yuan
authors.forename: Weiping
authors.initials: W
authors.lastname: Mao
authors.forename: Ling
authors.initials: L
authors.lastname: Yue
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Kong
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gao
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin