蛋白质硝基化修饰在心力衰竭发生发展中的作用

The role of protein nitration modification in the development and progression of heart failure

硝基化应激是指由一氧化氮或由其衍生的活性氮(RNS)与活性氧(ROS)联合发生的生物化学反应。在应激状态下,机体产生高浓度的超氧阴离子(O 2-)与一氧化氮,二者反应可生成过氧亚硝酸盐,使蛋白质酪氨酸残基发生硝基化修饰,生成3-硝基酪氨酸(3-NT)。3-NT通常用来反映蛋白质硝基化修饰的水平。蓄积的3-NT导致DNA损伤,引起细胞死亡,损害心脏结构,进而造成心脏功能障碍。心力衰竭是心血管疾病终末阶段出现的临床综合征,发病原因多样,具有发病率高、预后差的特点,是全世界范围内重要的公共卫生问题之一。在心力衰竭病理过程中,心脏的硝基化应激水平明显升高,大量蛋白质发生硝基化修饰,3-NT生成随之增加。本文对蛋白质硝基化修饰在心力衰竭发生发展中的作用做一综述。

Nitrative stress is a biochemical reaction that occurs in combination with reactive oxygen species(ROS)and nitric oxide or with active nitrogen species(RNS)derived from nitric oxide.Under stress,the body produces a high concentration of superoxide anion(O 2-)and nitric oxide,and the reaction of the two can produce peroxynitrite,which makes the protein tyrosine residue undergo nitration modification to produce 3-nitrotyrosine(3-NT).Therefore,3-NT is usually used to reflect the level of protein nitration modification.The accumulated 3-NT leads to DNA damage,cell death,cardiac structure damage,and cardiac dysfunction.Heart failure,a clinical syndrome that arises in the terminal stages of cardiovascular disease,is one of the important public health problems worldwide.The causes of heart failure are diverse,and it is characterized by high morbidity and poor prognosis.During the pathological process of heart failure,nitrative stress levels are markedly elevated in the heart,with a large number of proteins undergoing nitration modification and a concomitant increase in 3-NT production.This review focuses on the role of protein nitration modification in the development and progression of heart failure.