Opposing effects of delta and xi PKC in ethanol-induced cardioprotection.
Low amounts of ethanol reduce cardiac damage induced by ischemia. The protection from ischemic damage by acute exposure to low amounts of ethanol in isolated myocytes and intact heart have been attributed to activation of protein kinase C (PKC). We previously found that two PKC isozymes, delta and xi, are activated by ethanol in several cell models. Here, we perfused isozyme-selective agonist and antagonist peptides that we have generated into intact heart to determine the role of these two isozymes in ethanol-induced protection from transient ischemia. Whereas xi PKC activation was required for ethanol-induced protection, delta PKC activation led to further damage. These data explain the conflicting reports on the role of acute exposure to ethanol in protection from cardiac ischemia. The clinical implications of these findings are also discussed.
Chen
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Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mochly-Rosen
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D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D006335:Heart Injuries / Q000517:prevention & control*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000473:pathology*; D020011:Protective Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon
D002317:Cardiovascular Agents; D007527:Isoenzymes; D020011:Protective Agents; D000431:Ethanol; C497259:Prkcd protein, mouse; C497256:Prkce protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon