Heart attacks caused by occlusion of coronary arteries are often treated by mechanical or enzymatic removal of the occlusion and reperfusion of the ischemic heart. It is now recognized that reperfusion per se contributes to myocardial damage, and there is a great interest in identifying the molecular basis of this damage. We recently showed that inhibiting protein kinase C␦ (PKC␦) protects the heart from ischemia and reperfusion-induced damage. Here, we demonstrate that PKC␦ activity and

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... ndrial translocation at the onset of reperfusion mediates apoptosis by facilitating the accumulation and dephosphorylation of the pro-apoptotic BAD (Bcl-2-associated death promoter), dephosphorylation of Akt, cytochrome c release, PARP (poly(ADPribose) polymerase) cleavage, and DNA laddering. Our data suggest that PKC␦ activation has a critical proapoptotic role in cardiac responses following ischemia and reperfusion.