Cadmium activates CaMK-II and initiates CaMK-II-dependent apoptosis in mesangial cells.

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.