Signal Transduction in the Cardioprotective Effect of Alcohol

流行病学研究表明，轻度至中度使用乙醇与预防致命性冠状动脉疾病的保护作用有关。我们发现，乙醇的心脏保护作用需要腺苷A1受体在缺血时激活，像实验性缺血预处理（PC）。我们研究了这种保护的潜在下游介质，与PC相比。[1]PKC抑制剂白屈菜红碱是否能消除乙醇的保护作用？2.与对照组相比，暴露于乙醇的心肌细胞中的α、δ和ε蛋白激酶C（PKC）是否发生了易位？(1)白屈菜红碱可阻断乙醇对收缩恢复的促进作用。(2)Western blot分析和免疫荧光定位结果表明，有规律的乙醇摄入可引起εPKC持续移位，而δ或αPKC则无此作用。这种酶直接参与PC对缺血再灌注损伤的保护。这些发现表明：（i）规律的乙醇消耗通过εPKC的持续易位诱导长期的心脏保护作用;（ii）缺血时PKC活性是介导乙醇保护作用所必需的。[2]这种心脏保护作用是否由PC等物种特异性信号介导？腺苷受体阻断剂可阻断乙醇对豚鼠心脏的保护作用，但对大鼠心脏无影响。相比之下，α1-肾上腺素能阻滞剂在大鼠而不是豚鼠心脏中消除了乙醇的保护作用。这些发现与PC相似。[3]磷脂酶C（PLC）是否参与乙醇的心脏保护作用？阻断PLC可使乙醇对豚鼠心脏的保护作用消失，与PC相似。这些结果表明，乙醇的心脏保护作用可作为慢性缺血预处理用于临床。

Epidemiologic studies have shown that light to moderate ethanol use is associated with a protective effect against fatal coronary artery disease. We showed that the cardioprotective effect of ethanol requires adenosine A1 receptor activation at the time of ischemia, like experimental ischemic preconditioning (PC). We investigated the potential downstream mediators of this protection, compared with PC.[1] Is ethanol's protective effect abolished by PKC inhibitor, chelerythrine? 2. Are α,δandεprotein kinase C(PKC) translocated in myocytes from ethanol exposed hearts versus controls, like PC? (1) The improved contradtile recovery by ethanol was abolished by chelerythrine. (2) Western blot analysis and immunofluorescence localization demonstrate that regular ethanol consumption causes sustained translocation of εPKC, but not δor αPKC. This same enzyme is directly implicated in PC's protection against ischemia-reperfusion injury. These findings suggest (i) that regular ethanol consumption induces long-term cardioprotection through sustained translocation of εPKC and (ii) that PKC activity is necessary at the time of ischemia to mediate ethanol's protective effect.[2] Is the cardioprotective effect mediated by species-specific signaling like PC? Adenosine receptor blockade abolished ethanol's protection in guinea pig but not rat hearts. By contrast, α1-adrenergic blockade abolished ethanol's protection in rat but not guinea pig hearts. These finding are similar to PC.[3] Is phospholipase C(PLC) involved in the cardioprotective effect of ethanol? PLC blockade abolished ethanol's protection in guinea pig hearts, similar to PC.These results suggest that the cardioprotective effect of alcohol can be used for clinical application as a chronic ischemic preconditioning.