摘要
硝化应激(nitrative stress)指蛋白质的酪氨酸硝化,是一种重要的蛋白质翻译后修饰。近年来大量研究发现硝化应激在多种心血管疾病如缺血再灌注损伤、动脉粥样硬化、心力衰竭及高血压病等疾病的病理生理过程中起着关键作用。硝化应激是指由一氧化氮或由一氧化氮(?NO)衍生的活性氮族(reactive nitrogen species,RNS)与活性氧族共同联合发生的生物化学作用,使细胞内蛋白质中的酪氨酸硝化成3-硝基酪氨酸(3-nitrotyrosine,3-NT),引起细胞损伤或凋亡,从而对细胞产生多种毒性作用的病理状态,其最主要的两种途径是过氧亚硝酸根(ONOO-)途径和NO2-/H2O2/血红素过氧化物酶途径,反应为自由基机理。本文对硝化应激在多种心血管疾病发生发展中的作用及机制做了综述,指出蛋白质硝化具有选择性,特定酪氨酸残基发生硝化能够改变蛋白质的结构和功能,进一步鉴别体内的硝化蛋白,研究特定蛋白质硝化与疾病发生发展关系将为人类预防和治疗多种心血管疾病开辟新的途径。
Nitrative stress is an important posttranslational modification involving a variety of diseases.Many recent studies demonstrated that nitrative stress plays a key role in the pathophysiology of several major cardiovascular diseases such as myocardial ischemical reperfusion injury, atherosclerosis,heart failure,hypertension. nitration is a biological process derived from the biochemical interaction of nitric oxide or nitric oxide-derived secondary products ( RNS ) with reactive oxygen species,lead to the concomitant formation of tyrosyl radicals and?NO2,which combine at diffusion-controlled rates to form 3-nitrotyrosine,then lead cell damage or death,which cause many kinds of cytotoxic effects in cells.It is occurred via peroxynitrite or nitrite/hydrogen peroxide/hemeproxydase system,and nitrotyrosine is formed by free radical reaction. In this article,the role and mechanism of nitrative stress in several major cardiovascular diseases are reviewed.It points out that protein nitration has selectivity,and nitration of special tyrosine residue(s)can lead to the alteration of the structure and functions of the protein.Individual identification of nitrated proteins in vivo and investigation of the relation between special protein nitration and the development and progression of many cardiovascular diseases may open new avenues for the preventing and treatment of human cardiovascular diseases.
引文
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