title: Cadmium activates CaMK-II and initiates CaMK-II-dependent apoptosis in mesangial cells.
abstract: Cadmium is a toxic metal that initiates both mitogenic responses and cell death. We show that Cd(2+) increases phosphorylation and activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) in mesangial cells, in a concentration-dependent manner. Activation is biphasic with peaks at 1-5 min and 4-6 h. Cadmium also activates Erk, but this appears to be independent of CaMK-II. At 10-20 microM, Cd(2+) initiates apoptosis in 25-55% of mesangial cells by 6h. Inhibition of CaMK-II, but not of Erk, suppresses Cd(2+)-induced apoptosis. We conclude that activation of CaMK-II by Cd(2+) contributes to apoptotic cell death, independent of Erk activation.
authors: University of Toronto, Laboratory Medicine and Pathobiology, 1 King's College Circle, Toronto, Ont., Canada M5S 1A8.
authors: Ying
authors: Y
authors: Liu
authors: Douglas M
authors: DM
authors: Templeton
mesh_terms: D000818:Animals; D017209:Apoptosis; D002104:Cadmium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010766:Phosphorylation
chemical_list: D002413:Cations, Divalent; D002104:Cadmium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases