Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Basic Clin Pharmacol Toxicol. 2012 Jun;110(6):510-7. doi: 10.1111/j.1742-7843.2011.00843.x. Epub 2012 Jan 4.
Cadmium is a heavy metal that is known to cause toxicity to cells and, at low concentrations, can initiate apoptosis. This study was undertaken with the aim of defining the role of phospholipase C (PLC) in mediating cadmium-induced apoptosis in human embryonic kidney (HEK 293) cells. We have shown that intracellular Ca(2+) levels increased significantly in HEK 293 cells after 24-hr exposure to Cd. The activity of the calcium-dependent protease calpain rose by four times. The PLC-specific inhibitor, U73122, prevented the Cd-dependent increase in Ca(2+) levels and also abolished Cd-dependent calpain and caspase 3 activation as well as Cd-dependent mitochondrial Bax accumulation. Inhibition of PLC also leads to an increased cell viability following exposure to Cd. Taken together, the results show that the PLC pathway is involved in mediating Cd-induced apoptosis in HEK 293 cells.
镉是一种重金属，已知会对细胞造成毒性，在低浓度下，可引发细胞凋亡。本研究旨在确定磷脂酶 C（PLC）在介导人胚肾（HEK 293）细胞镉诱导凋亡中的作用。我们已经表明，镉暴露 24 小时后，HEK 293 细胞内 Ca(2+)水平显著升高。钙依赖性蛋白酶钙蛋白酶的活性增加了四倍。PLC 特异性抑制剂 U73122 可防止 Cd 依赖性 Ca(2+)水平升高，并消除 Cd 依赖性钙蛋白酶和半胱天冬酶 3 激活以及 Cd 依赖性线粒体 Bax 积累。PLC 的抑制也会导致暴露于 Cd 后细胞活力增加。综上所述，研究结果表明，PLC 途径参与介导 HEK 293 细胞镉诱导的凋亡。
