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蛋白质巯基亚硝基化参与调控一氧化氮介导的心肌缺血预适应

孙俊辉

美国国立卫生研究院心肺及血液研究所血管医学组.马里兰州 20892

摘要

一氧化氮(nitricoxide,NO)作为一种重要的信使分子参与缺血预适应(ischemic preconditioning,IPC)心肌保护。目前普遍认为NO通过经典的NO/cGMP依赖的信号转导途径调节线粒体ATP敏感性钾(ATP--sensitive potassium,K_(ATP))通道来发挥其保护作用,然而越来越多的数据表明NO还可能通过蛋白质巯基亚硝基化({sl S}--nitrosylation)来发挥生理功能。蛋白质巯基亚硝基化,即蛋白质半胱氨酸巯基与NO基团形成共价键,是一种氧化还原依赖的蛋白质翻译后可逆修饰。蛋白质巯基亚硝基化不仅可以改变蛋白质的结构和功能,而且还可以阻抑目标半胱氨酸的进一步氧化修饰。IPC增加{sl S}--亚硝基硫醇({sl S}--nitrosothiol)含量,引起蛋白质巯基亚硝基化。{sl S}--亚硝基硫醇还能发挥药理性预适应作用,抵抗心肌缺血/再灌注损伤。因此,蛋白质巯基亚硝基化是IPC心肌保护的一种重要途径,参与抵抗细胞内氧化应激和亚硝化应激(nitrosative stress)。

关键词： 巯基亚硝基化; 缺血预适应; 一氧化氮; 心肌保护

Protein {sl S}--nitrosylation: A role of nitric oxide signaling in cardiac ischemic preconditioning

Sun Junhui

Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

Abstract

Nitric oxide (NO) has been shown as an important signaling messenger involved in cardioprotection of ischemic preconditioning (IPC). To date, most studies suggest that NO might provide its protective effects by regulating the mitochondrial ATP-sensitive potassium (K_(ATP)) channel via the classic NO/cGMP-dependent pathway. However, there is emerging data suggesting that NO might also elicit its physiological role through protein S-nitrosylation. Protein S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl group(s) of cysteine residue(s) of proteins, is a reversible post-translational protein modification involved in redox-based cellular signaling. IPC has been found to increase S-nitrosothiol content and result in increased S-nitrosylation of proteins, which not only induces the structural and functional changes of modified proteins, but also prevents the target cysteine residue(s) from the further oxidative modification. In addition, S-nitrosothiols could elicit pharmacological preconditioning effect and protect against myocardial ischemia-reperfusion injury. Thus, protein S-nitrosylation is emerging as an important contributor to cardioprotection in IPC, providing protection from cellular oxidative and nitrosative stress,

Key words: S-nitrosylation;ischemic preconditioning;Nitric oxide;cardioprotection

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引用本文：

孙俊辉. 蛋白质巯基亚硝基化参与调控一氧化氮介导的心肌缺血预适应[J]. 生理学报 2007; 59 (5): 544-552.

Sun Junhui. Protein {sl S}--nitrosylation: A role of nitric oxide signaling in cardiac ischemic preconditioning. Acta Physiol Sin 2007; 59 (5): 544-552 (in Chinese with English abstract).