活性氧和NADPH氧化酶的结构特性及其对心肌细胞增殖与死亡的作用

活性氧和NADPH氧化酶的结构特性及其对心肌细胞增殖

与死亡的作用

李淼;王抒

【期刊名称】《中国组织工程研究》 【年(卷),期】2006(010)045

【摘要】目的:了解国内外在活性氧和NADPH氧化酶对细胞增殖与死亡作用机制方面的研究现状,并探讨活性氧和NADPH氧化酶在心肌细胞分化过程中的作用.资料来源:应用计算机检索Medline数据库1997-01/2003-12与活性氧和NADPH氧化酶对细胞增殖与死亡作用机制相关文章,检索词\oxygen

species\、\

oxidase\、\、

\、\限定文章语言种类为English.资料选择:纳入标准:①有关活性氧的产生和NADPH氧化酶结构活性以及它们对细胞增殖与死亡的作用机制.②有关心肌细胞分化的分子机制的研究.排除重复研究和综述性文章.资料提炼:共收集到132篇关于活性氧和NADPH氧化酶作用机制和心肌细胞分化的文章,其中有78篇符合纳入标准.资料综合:①活性氧参与众多疾病的发病机制主要源于线粒体内的电子传递链,而NADPH氧化酶与活性氧的产生密切相关;NADPH氧化酶是最早在吞噬细胞中发现,它是一种多酶复合物,其活性受胞内Ca2+浓度及该酶亚组分mRNA表达量的调节.②目前很多研究者认为氧化应激是一柄双刃剑,对细胞增殖和死亡起到双向调节的作用,而活性氧是这些效应信号传导过程中的第二信使;最近的资料显示,活性氧和NADPH氧化酶对心肌分化起到重要的调节作用,然而是何种NADPH氧化酶亚组分在心肌细胞中表达以及具体的调节通路还没有确切的结论,而这些问题的解决是深入

研究心肌细胞分化分子机制的关键.结论:活性氧包括超氧离子,过氧化氢和羟自由基,心肌细胞内活性氧的产生主要来自膜结合的NADPH氧化酶的催化作用.NADPH氧化酶依赖性的活性氧可作为第二信使参与细胞内多种信号传导途径.在心肌细胞中,活性氧通过这些途径双向调节细胞的增殖与死亡,而最近又发现活性氧在胚胎干细胞向心肌细胞分化过程中起重要的调节作用.对这些调节机制的研究有利于更好的认识活性氧及NADPH氧化化酶在心肌细胞分化中的重要作用并有利于确定促进心脏分化的因子.%OBJECTIVE: To recognize the research status on the mechanism of reactive oxygen species (ROS) and NADPH oxidases in cell growth and death,and explore the effects of ROS and NADPH oxidases on cardiomyocyte differentiation.DATA SOURCES: A computer-based online search of Medline was undertaken for the articles about the action mechanism of reactive oxygen and NADPH oxidases in cell growth and death published in English between January 1997 and December 2003 with the key words of \oxygen species, NADPH oxidase, Cardiomyocytes, Differentiation, Signal transduction\SELECTION: Inclusive criteria: ①Articles on ROS production and structure and activation of NADPH oxidase and their action mechanism in cell growth and death; ②Research about the molecule mechanism of cardiomyocytes differentiation. The repetitive research and review articles were excluded.DATA EXTRACTION: Totally 132 articles about the action mechanism of ROS and NADPH oxidase and cardiomyocytes differentiation were collected, and 78 ones met the

inclusive criteria.DATA SYNTHESIS: ①ROS involved in pathogenesis of many diseases were mainly from intramitochondrial electron transport chains, and NADPH oxidase was closely related with ROS production; NADPH oxidase firstly found in phagocyte was a kind of multienzyme complex, and its activity was regulated by the concentration of Ca2+ in cells and mRNA expression of its subunits. ②At present, many researchers presumed that oxidative stress was a double-edged sword, and it two-ways regulated the cell proliferation and death, in which ROS served as the second messenger in the signal transduction. Recent data showed that ROS and NADPH oxidase played important roles in cardiomyocytes differentiation; however, it was not identified which subunit of NADPH oxidase expressed in myocardial cells and its detail regulative pathway. Those problems were important for further study in the

molecule

mechanism

of

cardiomyocytes

differentiation.CONCLUSION: ROS including superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH-), are generated in cardiomyocytes mainly by a membrane-bound NADPH oxidase (NOX). The NOX-derived ROS, as the second passenger, play important roles in various intracellular signaling pathways. In cardiomyocytes, ROS have the potential to alter the balance between cell growth and death through

these

signaling

pathways.

Recently,ROS

have

been

demonstrated to play a critical role in regulation of cardiomyocyte