δPKC-mediated activation of εPKC in ethanol-induced cardiac protection from ischemia

Previous studies have demonstrated that acute ethanol exposure induces activation of δ protein kinase C (δPKC) and εPKC, and mimics ischemic preconditioning via εPKC activation. However, the role of δPKC isozyme in ischemia and reperfusion is still controversial. Here, we investigated the role of δPKC in ethanol-induced cardioprotection using a selective δPKC activator (ψδRACK), or inhibitor (δV1-1), and a selective εPKC inhibitor (εV1-2) in isolated mouse hearts. Mice were injected intraperitoneally or by gavage with ethanol, regulators of δ and εPKC or an adenosine A1 receptor blocker (DPCPX). Isolated perfused mouse hearts were subjected to a 30-min global ischemia and a 120-min reperfusion, ex vivo. Injection of 0.5 g/kg ethanol 1 h, but not 10 min, before ischemia reduced infarct size and CPK release. Pretreatment with εV1-2 abolished this ethanol-induced cardioprotection. Pretreatment with δV1-1 induced cardioprotection when injected with ethanol (0.5 g/kg) 10 min before ischemia, but δV1-1 partly inhibited ethanol-induced cardioprotection when injected with ethanol 1-h before the onset of ischemia. ψδRACK injection 1 h, but not 10 min, before ischemia induced cardioprotection and translocation of εPKC from the cytosol to the particulate fraction. Pretreatment with DPCPX or εV1-2 inhibited ψδRACK-induced cardioprotection and translocation of εPKC. Therefore, activation of δPKC-induced by ethanol or by the δPKC activator is cardioprotective, provided that sufficient time passes to allow δPKC-induced activation of εPKC, an A1 adenosine receptor-dependent process.