收稿日期: 2008-03-31
修回日期: 2008-08-12
网络出版日期: 2009-03-15
基金资助
国家自然科学基金(30470374)、中国科学院院长基金和中国科学院研究生院启动基金资助项目
Protein homocysteinylation and mechanisms of atherosclerosis
Received date: 2008-03-31
Revised date: 2008-08-12
Online published: 2009-03-15
动脉粥样硬化是严重危害人类生命健康的世界性疾病,因发病机制至今未明,尚无有效防治措施.大量研究证明,高同型半胱氨酸血症是引起动脉粥样硬化的独立危险因素.高同型半胱氨酸血症与氧化应激、内质网应激、血管内皮细胞损伤及血液粘稠度增高之间的密切关系已有大量文献报道,但其具体机制有待阐明.综述简要介绍了近年来在国际上颇受关注的蛋白质同型半胱氨酸化.围绕抗氧化酶、内质网蛋白、凝血因子、低密度脂蛋白,以及与钙信号有关的蛋白被同型半胱氨酸化的研究发现,从同型半胱氨酸及其衍生物同型半胱氨酸巯基内酯对蛋白质的共价修饰反应,到使分子结构与理化性质发生改变的生化机制,阐述了这种修饰与动脉粥样硬化斑块形成的关系.
吴云飞 , 钟良玮 . 蛋白质同型半胱氨酸化与动脉粥样硬化机制[J]. 中国科学院大学学报, 2009 , 26(2) : 145 -151 . DOI: 10.7523/j.issn.2095-6134.2009.2.001
Atherosclerosis is a world-wide disease with severe effects on human health. Although it remains unclear about the pathological mechanisms of atherosclerosis that can not be efficiently prevented and treated so far, a large body of evidence suggests that increased level of plasma homocysteine is an independent risk factor for atherosclerosis. Numerous studies have found a close relationship between hyperhomocysteinemia and oxidative stress, endoplasmic reticulum stress, endothelial cell injury as well as increased viscosity of blood, but the underlying mechanisms are largely unknown. This brief review introduces protein homocysteinylation, to which more and more researchers abroad begin to pay attention. We mainly focus on homocysteinylation of antioxidant enzymes, endoplasmic reticulum resident proteins, coagulation factors, low-density lipoprotein and calcium signaling-related proteins. To elucidate an importance of protein homocysteinylation in the development of atherosclerotic plaque, we also describe how homocysteine and its derivative homocysteine thiolactone covalently modify proteins, by which the structure and physical-chemical properties of target molecules are altered.
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