
Activation of ɛ protein kinase C correlates with a cardioprotective effect of regular ethanol consumption
Author(s) -
Masami Miyamae,
Manuel M. Rodriguez,
S. Albert Camacho,
Ivan Diamond,
Daria MochlyRosen,
Vincent M. Figueredo
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.14.8262
Subject(s) - cardioprotection , chelerythrine , ischemia , reperfusion injury , pharmacology , creatine kinase , ischemic preconditioning , medicine , protein kinase c , myocardial infarction , ethanol , cardiology , chemistry , kinase , biochemistry
In addition to decreasing the incidence of myocardial infarction, recent epidemiological data suggest that regular alcohol consumption improves survival after myocardial infarction. We recently found that chronic ethanol exposure induces long-term protection against cardiac ischemia–reperfusion injury, which improves myocardial recovery after infarction. Furthermore, this cardioprotection by ethanol is mediated through myocyte adenosine A1 receptors. We now determine the role of protein kinase C (PKC) in ethanol’s protective effect against ischemia–reperfusion injury. Using perfused hearts of ethanol-fed guinea pigs, we find that improved contractile recovery and creatine kinase release after ischemia–reperfusion are abolished by PKC inhibition with chelerythrine. Western blot analysis and immunofluorescence localization demonstrate that regular ethanol consumption causes sustained translocation (activation) of ɛPKC, but not δ or αPKC. This same isozyme is directly implicated in ischemic preconditioning’s protection against ischemia–reperfusion injury. Our findings suggest (i ) that regular ethanol consumption induces long-term cardioprotection through sustained translocation of ɛPKC and (ii ) that PKC activity is necessary at the time of ischemia to mediate ethanol’s protective effect against ischemia–reperfusion injury. Studying this selective effect of ethanol on ɛPKC activation may lead to new therapies to protect against ischemia–reperfusion injury in the heart and other organ systems.