Signal Transduction in the Cardioprotective Effect of Alcohol

流行病学研究表明，轻度到中度的酒精使用与预防致命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在缺血时激活腺苷A1受体，就像实验性的缺血预适应(PC)一样。[1]乙醇的保护作用是否被蛋白激酶C抑制剂白屈菜红碱所消除？2.α，δ和ε蛋白激酶C(PKC)在乙醇处理的心肌细胞中与对照组(如PC)相比是否有转位？(1)白屈菜红碱可消除乙醇促进心肌细胞损伤恢复的作用。(2)免疫印迹分析和免疫荧光定位显示，规律饮酒可引起ε蛋白激酶C的持续性易位，但不能引起δ或α蛋白激酶C的持续易位。这种酶直接参与了PC对缺血再灌注损伤的保护作用。这些发现表明：(I)经常饮酒通过ε蛋白激酶C的持续移位而诱导长期的心脏保护，以及(Ii)在缺血时，蛋白激酶C的活性是必要的，以介导乙醇的保护作用。[2]这种心脏保护作用是否像PC一样由物种特异性信号介导？腺苷受体阻断可消除乙醇对豚鼠心脏的保护作用，但不能消除大鼠心脏的保护作用。相反，α1肾上腺素能受体阻滞剂取消了乙醇对大鼠心脏的保护作用，但不能消除豚鼠心脏的保护作用。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可阻断乙醇对豚鼠心脏的保护作用，与PC相似。这些结果表明，乙醇的心脏保护作用可作为一种慢性缺血预适应应用于临床。

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.