Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism

Heat shock produces cellular tolerance to a variety of adverse conditions; however, the protective effect of heat shock on renal cell ischemic injury remains unclear. Protein kinase C (PKC) has been implicated in the signalin g mechanisms of acute preconditioning, yet it remains unknown whether PKC m ediates heat shock-induced delayed preconditioning in renal cells. To study this, renal tubular cells (LLC-PK1) were exposed to thermal stress (43 deg reesC) for 1 h and heat shock protein (HSP) 72 induction was confirmed by W estern blot analysis. Cells were subjected to simulated ischemia 24 h after thermal stress, and the effect of heat shock (delayed preconditioning) on ischemia-induced apoptosis (terminal deoxynucleotidyl transferase dUTP nick -end labeling) and B cell lymphoma 2 (Bcl(2)) expression (Western) was dete rmined. Subsequently, the effect of PKC inhibition on HSP72 induction and h eat stress-induced ischemic tolerance was evaluated. Thermal stress induced HSP72 production, increased Bcl2 expression, and prevented simulated ische mia-induced renal tubular cell apoptosis. PKC inhibition abolished thermal induction of HSP72 and prevented heat stress-induced ischemic tolerance. Th ese data demonstrate that thermal stress protects renal tubular cells from simulated ischemia-induced apoptosis through a PKC-dependent mechanism.