Miyamae M, Rodriguez M M, Camacho S A, Diamond I, Mochly-Rosen D, Figueredo V M
Department of Medicine (Cardiology), San Francisco General Hospital, San Francisco, CA, 94110, USA.
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8262-7. doi: 10.1073/pnas.95.14.8262.
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 epsilonPKC, but not delta or alphaPKC. 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 epsilonPKC 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 epsilonPKC activation may lead to new therapies to protect against ischemia-reperfusion injury in the heart and other organ systems.
除了降低心肌梗死的发生率外，最近的流行病学数据表明，经常饮酒可提高心肌梗死后的生存率。我们最近发现，长期乙醇暴露可诱导对心脏缺血再灌注损伤的长期保护作用，从而改善梗死后的心肌恢复。此外，乙醇的这种心脏保护作用是通过心肌细胞腺苷A1受体介导的。我们现在确定蛋白激酶C（PKC）在乙醇对缺血再灌注损伤的保护作用中的作用。使用乙醇喂养的豚鼠的灌注心脏，我们发现用白屈菜红碱抑制PKC可消除缺血再灌注后收缩恢复和肌酸激酶释放的改善。蛋白质印迹分析和免疫荧光定位表明，经常饮酒会导致εPKC持续易位（激活），但不会导致δ或αPKC易位。同一种同工酶直接参与缺血预处理对缺血再灌注损伤的保护作用。我们的研究结果表明：（i）经常饮酒通过εPKC的持续易位诱导长期心脏保护作用；（ii）缺血时PKC活性对于介导乙醇对缺血再灌注损伤的保护作用是必要的。研究乙醇对εPKC激活的这种选择性作用可能会带来新的疗法，以预防心脏和其他器官系统的缺血再灌注损伤。
