Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, PR China.
Environ Toxicol Pharmacol. 2010 Sep;30(2):202-8. doi: 10.1016/j.etap.2010.06.004. Epub 2010 Jul 21.
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.
镉是一种众所周知的对肾脏有毒的金属。谷胱甘肽 S-转移酶 P1（GSTP1）在解毒和外源化学物质代谢中起着重要作用。在这里，我们研究了 GSTP1 是否会影响人胚肾细胞系（HEK）293 细胞中 Cd（2+）诱导的凋亡细胞死亡。结果表明，在 HEK293 细胞中，通过 RNA 干扰沉默 GSTP1 表达会增强 Cd（2+）诱导的细胞活力丧失。GSTP1 的过表达抑制了线粒体膜电位的丧失，阻止了细胞色素 c 从线粒体释放和 caspase-3 的激活，抑制了丝裂原激活的蛋白激酶（MAPKs）包括 ERK、JNK 和 p38，并抑制了 Cd（2+）诱导的细胞凋亡。寡核苷酸体 DNA 片段化分析还表明，腺病毒感染过表达 GSTP1 可防止 Cd（2+）诱导的原代肾小管细胞凋亡。我们的数据表明，GSTP1 是 Cd（2+）诱导细胞凋亡的内源性抑制剂。
