title: Phospholipase C mediates cadmium-dependent apoptosis in HEK 293 cells.
abstract: 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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. tolekan@hotmail.com
authors.forename: Akeem O
authors.initials: AO
authors.lastname: Lawal
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Ellis
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019256:Cadmium Chloride / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D009336:Necrosis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D051028:bcl-2-Associated X Protein; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010738:Type C Phospholipases; C505407:CASP3 protein, human; D002154:Calpain; D053148:Caspase 3; D019256:Cadmium Chloride; D002118:Calcium