Opening of mitochondrial K(ATP) channels triggers cardioprotection. Are reactive oxygen species involved?
Opening of mitochondrial K(ATP) channels triggers cardioprotection. Are reactive oxygen species involved?
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线粒体 K(ATP) 通道的开放可触发心脏保护作用。
DOI：
10.1161/hh0801.090537
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发表时间：
2001
影响因子：
20.1
通讯作者：
B. O’Rourke
中科院分区：
文献类型：
--
作者：
Y. Liu;B. O’Rourke
缺血预处理是一种缺血和再灌注的短暂发作自相矛盾地保护心脏免受随后的致死性缺血的现象，1已在概念上分为触发器和介质/效应器。2 3触发器在指标缺血之前起作用，随后在致死性缺血期间保护介质/效应器。已知的触发因素包括腺苷受体、α1-肾上腺素能受体和阿片受体的激活、细胞内Ca 2+升高和活性氧（ROS）增加。2线粒体ATP依赖性钾通道已经提出mitoKATP是这种保护作用的介质。4触发器和效应器之间的联系可能是蛋白激酶的激活这些激酶可使mitoKATP磷酸化，导致通道早期开放和/或在更大程度上减少致死性缺血期间的损伤。有趣的是，mitoKATP的开放也可以触发心脏保护作用。缺血前用mitoKATP开放剂二氮嗪短暂处理的心脏梗死明显较小。3 5二氮嗪的触发作用可被蛋白激酶C5 6和酪氨酸激酶抑制剂阻断，3表明二氮嗪激活蛋白激酶，与其他触发剂作用相似。当ROS清除剂与二氮嗪共同给药时，这种作用消失。3已知ROS可激活蛋白激酶并作为一种代谢物。2因此，Pain等人3提出，二氮嗪打开mitoKATP可能会增加ROS。
在本期《循环研究》中，福布斯等人7直接证明了在离体大鼠心室肌细胞中，mitoKATP的开放增加了ROS的产生。使用ROS敏感的荧光探针2′，7 ′-二氯荧光素（DCF），他们发现二氮嗪和吡那地尔（一种非选择性KATP开放剂）增加DCF荧光，这意味着ROS水平升高。
Ischemic preconditioning, a phenomenon in which brief episodes of ischemia and reperfusion paradoxically protect the heart against subsequent lethal ischemia,1 has been conceptually divided into triggers and mediators/effectors.2 3 The trigger, which acts before the index ischemia, is followed by the protection of mediators/effectors during the lethal ischemia. Known triggers include activation of adenosine receptors, α1-adrenegic receptors and opioid receptors, elevated intracellular Ca2+, and increased reactive oxygen species (ROS).2 The mitochondrial ATP-dependent potassium channel (mitoKATP) has been proposed to be the mediator of this protection.4 The link between the trigger and effector may be the activation of protein kinases (eg, protein kinase C, tyrosine kinase, and downstream kinases), which may phosphorylate mitoKATP, causing the channel to open early and/or to a greater extent to reduce injury during the lethal ischemia. Interestingly, opening of mitoKATP can also trigger cardioprotection. Hearts treated with the mitoKATP opener diazoxide for a brief period before ischemia had significantly smaller infarction.3 5 The triggering effect from diazoxide can be blocked by protein kinase C5 6 and tyrosine kinase inhibitors,3 suggesting that diazoxide activates protein kinases, acting similarly to other triggers. This effect was lost when ROS scavengers were coadministrated with diazoxide.3 ROS are known to activate protein kinases and act as a trigger.2 Thus, it was proposed by Pain et al3 that the opening of mitoKATP by diazoxide may increase ROS.
In this issue of Circulation Research , Forbes et al7 provide a direct demonstration that opening of mitoKATP increases ROS production in isolated rat ventricular myocytes. Using a ROS-sensitive fluorescent probe 2′,7′-dichlorofluorescin (DCF), they showed that diazoxide as well as pinacidil (a nonselective KATP opener) increased DCF fluorescence, implying an elevated ROS …
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腺苷 A1 受体激活可减少活性氧并减弱心室肌细胞的击晕作用。
影响因子：
5
作者：
Narayan,P;MentzerJr,RM;Lasley,RD
通讯作者：
Lasley,RD
影响因子：
37.8
作者：
Liu, YG;Sato, T;Marban, E
通讯作者：
Marban, E
影响因子：
20.1
作者：
Vanden Hoek, TL;Becker, LB;Schumacker, PT
通讯作者：
Schumacker, PT
影响因子：
37.8
作者：
Sato, T;Sasaki, N;Marbán, E
通讯作者：
Marbán, E
蛋白激酶 C 在线粒体 KATP 通道介导的大鼠心肌 Ca2 超载损伤保护中的作用。
影响因子：
20.1
作者：
Wang,Y;Ashraf,M
通讯作者：
Ashraf,M