Signal Transduction in the Cardioprotective Effect of Alcohol

酒精心脏保护作用中的信号转导

基本信息

批准号：
10670683
负责人：
MIYAMAE Masami
金额：
$ 1.98万
依托单位：
Osaka Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670683/
关键词：
ischemia reperfusion alcohol protein kinase C phospholipase C adenosine preconditioning protein kinase C ラット

项目摘要

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.

流行病学研究表明，光到中度乙醇的使用与针对致命冠状动脉疾病的保护作用有关。我们表明，乙醇的心脏保护作用需要在缺血时腺苷A1受体激活，例如实验性缺血性预处理（PC）。与PC相比，我们研究了该保护的潜在下游介质。[1] PKC抑制剂Chelerythrine是否废除了乙醇的保护作用？ 2。是否在乙醇暴露的心脏与对照（如PC）中翻译在肌细胞中的α，ΔANDεPROTEIN激酶C（PKC）？（1）Chelerythrine废除了乙醇的矛盾恢复的改善。（2）Western印迹分析和免疫荧光定位表明，常规乙醇消耗会导致εpkc的持续易位，但不会导致ΔORαPKC。同样的酶直接与PC防御缺血再灌注损伤有关。这些发现表明（i）常规的乙醇消耗通过εPKC的持续易位诱导长期心脏保护，并且（ii）在缺血时需要PKC活性来介导乙醇的保护作用。[2] [2]心脏保护作用是否由PC（例如PC）特定于规格的信号介导？腺苷接收器封锁废除了几内亚猪的乙醇保护，而不是大鼠的心。相比之下，α1-肾上腺素阻塞废除了大鼠但豚鼠心脏中的乙醇保护。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？ PLC封锁废除了类似于PC的豚鼠心中乙醇的保护。这些结果表明，酒精的心脏保护作用可用于临床应用，作为慢性缺血预处理。