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Bcl-2 家族蛋白和半胱氨酸天冬氨酸蛋白酶在细胞凋亡调控中的作用。

Role of Bcl-2 family proteins and caspases in the regulation of apoptosis.

机构信息

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, KSA.

出版信息

Mol Cell Biochem. 2011 May;351(1-2):41-58. doi: 10.1007/s11010-010-0709-x. Epub 2011 Jan 6.

Abstract

Apoptosis, or programmed cell death, plays a pivotal role in the elimination of unwanted, damaged, or infected cells in multicellular organisms and also in diverse biological processes, including development, cell differentiation, and proliferation. Apoptosis is a highly regulated form of cell death, and dysregulation of apoptosis results in pathological conditions including cancer, autoimmune and neurodegenerative diseases. The Bcl-2 family proteins are key regulators of apoptosis, which include both anti- and pro-apoptotic proteins, and a slight change in the dynamic balance of these proteins may result either in inhibition or promotion of cell death. Execution of apoptosis by various stimuli is initiated by activating either intrinsic or extrinsic pathways which lead to a series of downstream cascade of events, releasing of various apoptotic mediators from mitochondria and activation of caspases, important for the cell fate. In view of recent research advances about underlying mechanism of apoptosis, this review highlights the basics concept of apoptosis and its regulation by Bcl-2 family of protein. Furthermore, this review discusses the interplay of various apoptotic mediators and caspases to decide the fate of the cell. We expect that this review will add to the pool of basic information necessary to understand the mechanism of apoptosis which may implicate in designing better strategy to develop biomedical therapy to control apoptosis.

摘要

细胞凋亡,又称程序性细胞死亡,在多细胞生物中清除不需要的、受损的或感染的细胞以及在多种生物学过程中发挥关键作用,包括发育、细胞分化和增殖。细胞凋亡是一种高度调控的细胞死亡形式,细胞凋亡的失调导致包括癌症、自身免疫和神经退行性疾病在内的病理状况。Bcl-2 家族蛋白是细胞凋亡的关键调节因子,包括抗凋亡和促凋亡蛋白,这些蛋白的动态平衡的微小变化可能导致细胞死亡的抑制或促进。各种刺激引发的细胞凋亡的执行是通过激活内在或外在途径来启动的,这些途径导致一系列下游级联事件,从线粒体释放各种凋亡介质并激活半胱天冬酶,这对细胞命运很重要。鉴于细胞凋亡的潜在机制的最新研究进展,本综述强调了细胞凋亡的基本概念及其受 Bcl-2 家族蛋白的调控。此外,本综述讨论了各种凋亡介质和半胱天冬酶的相互作用,以决定细胞的命运。我们希望本综述将增加理解细胞凋亡机制所需的基础知识,这可能有助于设计更好的生物医学治疗策略来控制细胞凋亡。

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