Cd damages kidney PT by radical formation and results in apoptosis. Apoptosis involves calpain activation after 6 h 10 mM Cd exposure in PT cells (W.K. Lee et al. 2006 Am J Physiol 291:F823). The sphingolipid Cer mediates oxidative stress induced cell death. Therefore we investigated the role of Cer in Cd induced apoptosis of PT cells.

Exposure of PT cells to 10-50 mM Cd for 3-6 h caused 3-5% apoptosis as determined by Hoechst 33342/ethidium bromide nuclear staining. 50 mM Cd elevated endogenous Cer formation, measured by a diacylglycerol kinase assay and thin layer chromatography, by ~25% (3 h) and ~75% (24 h). Depletion of sphingolipid pools by 3 mM fumonisin B 1 (FB1) abolished 3 h 50 mM Cd induced Cer formation and decreased apoptosis caused by 10-50 mM Cd for 3 h. To ascertain whether calpains were a downstream target of Cer, calpain activity in PT cells was measured following 10 mM Cd for 6 h ± FB 1. Indeed FB1 significantly attenuated Cd induced calpain activity.

We conclude that Cd induced apoptosis of kidney PT cells entails endogenous Cer elevation and subsequent calpain activation, which may propagate kidney damage by Cd.

Funded by DFG TH 345/8-1