αB-晶状体蛋白抗细胞凋亡的机制研究

发布时间：2018-01-11 13:15

本文关键词：αB-晶状体蛋白抗细胞凋亡的机制研究　出处：《中南大学》2005年博士论文　论文类型：学位论文

【摘要】： 心血管疾病(CVD)是目前我国人群死亡的首位原因,其发病率和死亡率呈逐年上升的趋势。近年来大量研究表明,心肌细胞凋亡涉及许多心血管疾病的发生发展,而氧化应激/损伤在其中发挥重要作用。作为终末分化细胞,心肌细胞凋亡的累积效应将导致其数量减少和心功能的降低,促进心力衰竭的发生发展。因此,干预心肌细胞凋亡是目前心血管疾病防治研究中的一项重要课题。细胞凋亡的发生机制主要涉及两条信号转导通路,即线粒体通路和膜死亡受体通路。近年来对线粒体凋亡通路的研究已成为凋亡研究中的热点和前沿。研究发现,氧化应激等因素可促使线粒体外膜通透性增加,促进膜间隙中的促凋亡分子如cytochrome C、Smac/DIABLO、AIF、Endo G和多种caspases等的释放,这些促凋亡分子继而通过不同的下游机制导致细胞凋亡。另一方面,线粒体信号通路又受到细胞中多种Bcl-2家族蛋白、转录因子(如p53、NF-κB)和热休克蛋白等细胞内蛋白的影响和调控。近年来大量研究表明,多种热休克蛋白(如HSP70、HSP90、HSP27)可作用于凋亡信号通路的不同环节和不同水平发挥抗凋亡的细胞保护功能。作为小分子热休克蛋白家族主要成员,αB-晶状体蛋白在成年心肌组织中的相对高表达提示其具有重要的生物学意义。近年来在肿瘤细胞、晶
[Abstract]:Cardiovascular disease (CVD) is the leading cause of death in China, and its morbidity and mortality are increasing year by year. Cardiomyocyte apoptosis is involved in the occurrence and development of many cardiovascular diseases, and oxidative stress / injury plays an important role in it. The cumulative effect of cardiomyocyte apoptosis will lead to the decrease of its number and cardiac function, and promote the occurrence and development of heart failure. Intervention of cardiomyocyte apoptosis is an important subject in the prevention and treatment of cardiovascular disease. The mechanism of apoptosis mainly involves two signal transduction pathways. In recent years, the study of mitochondrial apoptosis pathway has become a hot spot and frontier in the research of apoptosis. It has been found that oxidative stress and other factors can promote the increase of mitochondrial outer membrane permeability. To promote the release of apoptosis-promoting molecules such as cytochrome Con / DIABLON AIF-Endo G and various caspases in the membrane space. These pro-apoptotic molecules in turn lead to apoptosis through different downstream mechanisms. On the other hand, mitochondrial signaling pathways are subjected to a variety of Bcl-2 family proteins, transcription factors (such as p53) in the cells. Effects and regulation of intracellular proteins such as NF- 魏 B) and heat shock proteins. In recent years a large number of studies have shown that a variety of heat shock proteins (such as HSP70 HSP90). HSP27 can act on different links and levels of apoptotic signaling pathway and play a role in cell protection against apoptosis. HSP27 is a major member of the heat shock protein family of small molecules. The relatively high expression of 伪 B-crystallin in adult myocardium suggests that it has important biological significance.
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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