Implication of protein kinase C-alpha, delta, and epsilon isoforms in ischemic preconditioning in perfused rat hearts

Ischemic preconditioning is a phenomenon in which one or several cycle(s) of brief ischemia-reperfusion protects the myocardium against the cell injury caused by subsequent prolonged ischemia. Protein kinase C (PKC) inhibitors blunt the cardioprotection arising from ischemic preconditioning. To investigate which PKC isoform is involved in ischemic preconditioning, we identified the PKC isoform that translocates to the membrane fraction by means of immunoblotting with specific antibodies. PKC-alpha, delta, epsilon isoforms all increased in the membrane fraction after three cycles of 3 min ischemia and 5 min reperfusion (ischemic preconditioning) in the perfused rat heart. The ischemic preconditioning significantly improved the recovery of left ventricular developed pressure (LVDP) during reperfusion following 20 min of ischemia. A PKC specific inhibitor, chelerythrine (1.0 microM) blocked the effect of ischemic preconditioning on LVDP recovery and the translocation of PKC-alpha, delta, epsilon isoforms. These data suggest that one or more of these three isoforms of PKC is involved in ischemic preconditioning by phosphorylating membrane proteins.