ACTIVATION OF EPSILON-PROTEIN-KINASE-C CORRELATES WITH A CARDIOPROTECTIVE EFFECT OF REGULAR ETHANOL-CONSUMPTION

In addition to decreasing the incidence of myocardial infarction, rece nt epidemiological data suggest that regular alcohol consumption impro ves survival after myocardial infarction, We recently found that chron ic ethanol exposure induces long-term protection against cardiac ische mia-reperfusion injury, which improves myocardial recovery after infar ction. Furthermore, this cardioprotection by ethanol is mediated throu gh myocyte adenosine A(1) receptors, We now determine the role of prot ein kinase C (PKC) in ethanol's protective effect against ischemia-rep erfusion injury. Using perfused hearts of ethanol-fed guinea pigs, we find that improved contractile recovery and creatine kinase release af ter ischemia-reperfusion are abolished by PKC inhibition with cheleryt hrine, Western blot analysis and immunofluorescence localization demon strate that regular ethanol consumption causes sustained translocation (activation) of epsilon PKC, but not delta or alpha PKC. This same is ozyme is directly implicated in ischemic preconditioning's protection against ischemia-reperfusion injury. Our findings suggest (i) that reg ular ethanol consumption induces long-term cardioprotection through su stained translocation of epsilon PKC and (ii) that PKC activity is nec essary at the time of ischemia to mediate ethanol's protective effect against ischemia-reperfusion injury. Studying this selective effect of ethanol on epsilon PKC activation may lead to new therapies to protec t against ischemia-reperfusion injury in the heart and other organ sys tems.