Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Circ Res. 2010 Mar 5;106(4):633-46. doi: 10.1161/CIRCRESAHA.109.207381.
Well over 2 decades have passed since the endothelium-derived relaxation factor 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, endothelium-derived relaxation factor activity (ie, 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. Furthermore, 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.
自报道内皮衍生松弛因子是气态分子一氧化氮（NO）以来，已经过去了 20 多年。尽管可溶性鸟苷酸环化酶（它产生环鸟苷单磷酸，cGMP）是第一个被识别的 NO 受体，但越来越明显的是，NO 以不依赖 cGMP 的方式发挥普遍影响。特别是，NO 的许多（如果不是大多数）作用是通过 S-亚硝基化介导的，即 NO 基团将蛋白质半胱氨酸巯基共价修饰生成 S-亚硝基硫醇（SNO）。此外，在当前的 NO 生物学框架内，内皮衍生松弛因子活性（即 G 蛋白偶联受体介导或剪切诱导的内皮衍生 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物。此外，S-亚硝基化在 NO 在心血管系统中的几乎所有主要功能中都具有重要作用。在这里，我们回顾了 S-亚硝基化（和去亚硝基化）的基本生物化学，讨论了 S-亚硝基化在 NO 的血管和心脏功能中的作用，并确定了当前和潜在的临床应用。
