S-nitrosylation in cardiovascular signaling.
S-nitrosylation in cardiovascular signaling.
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DOI：
10.1161/circresaha.109.207381
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发表时间：
2010-03-05
影响因子：
20.1
通讯作者：
Stamler JS
中科院分区：
文献类型：
--
作者：
Lima B;Forrester MT;Hess DT;Stamler JS
自从内皮细胞衍生的松弛因子(EDRF)被报道为气态分子一氧化氮(NO)以来，已经过去了二十多年。尽管可溶性鸟苷环化酶(CGMP)是第一个被发现的NO受体，但人们越来越清楚地发现，NO以cGMP非依赖的方式对机体产生普遍的影响。特别是，NO的许多作用(如果不是大多数的话)是由S亚硝化介导的，亚硝化是蛋白质半胱氨酸硫醇被NO基团共价修饰生成S亚硝硫醇(SNO)。此外，在目前的NO生物学框架内，EDRF的活性--即G蛋白偶联受体介导的，或剪切诱导的内皮衍生的NO生物活性--被认为涉及SNO的核心作用，既作为第二信使又作为信号效应器。此外，在心血管系统中，几乎所有NO的主要功能都涉及到S-亚硝化的重要作用。本文综述了S-亚硝化(和反硝化)的基本生物化学，讨论了S-亚硝化在NO的心血管和心脏功能中的作用，并确定了目前和潜在的临床应用。
Well over two decades has passed since the endothelium-derived relaxing factor (EDRF) was reported to be the gaseous molecule nitric oxide (NO). Although soluble guanylyl cyclase (which generates cyclic guanosine monophosphate, cGMP) was the first identified receptor for NO, it has become increasingly clear that NO exerts a ubiquitous influence in a cGMP-independent manner. In particular, many if not most effects of NO are mediated by S-nitrosylation, the covalent modification of a protein cysteine thiol by an NO group to generate an S-nitrosothiol (SNO). Moreover, within the current framework of NO biology, EDRF activity—i.e. G-protein coupled receptor-mediated, or shear-induced endothelium-derived NO bioactivity—is understood to involve a central role for SNOs, acting both as second messengers and signal effectors. Further, essential roles for S-nitrosylation have been implicated in virtually all major functions of NO in the cardiovascular system. Here we review the basic biochemistry of S-nitrosylation (and denitrosylation), discuss the role of S-nitrosylation in the vascular and cardiac functions of NO and identify current and potential clinical applications.