Bcl-2蛋白家族和p53基因在细胞凋亡中的调控效应

Effect of Bcl-2 protein family and p53 gene on regulating and controlling cell apoptosis

目的:细胞凋亡是个体发育过程中由一系列基因控制的细胞主动死亡过程。在多数细胞类型中,原癌基因Bcl-2蛋白家族与p53是重要的细胞凋亡调节因子,在细胞凋亡中相互联系,相互作用,从而调控细胞凋亡。文章探讨Bcl-2蛋白家族和p53基因对细胞凋亡的调控机制。资料来源:引用计算机检索1995/2006PubMed、Springer link的相关文章,检索词“apoptosis,Bcl-2protein family,p53”,并限定文章语言种类为English。同时计算机检索1995/2006中国期刊全文数据库或万方数据库的相关文章,检索词为“凋亡,Bcl-2,Bax”,限定文章语言种类为中文。并手工检索《细胞凋亡基础与临床》。资料选择:对资料进行初审,被选文献符合以下标准:①Bcl-2蛋白家族与凋亡的关系。②p53基因与凋亡的关系。③细胞凋亡基因调控的研究。④Bcl-2蛋白家族、p53基因调节细胞凋亡的机制研究。排除重复研究。资料提炼:共收集到70篇相关文献,中文文献均为全文,大部分外文文献为全文,其他为摘要。入选关于Bcl-2蛋白家族、p53基因与凋亡的关系及机制,细胞凋亡基因调控的相关文献32篇。资料综合:①Bcl-2蛋白家族是细胞凋亡相关基因研究得最多的一类蛋白质。包含抑制和促进细胞凋亡两类功能相反的蛋白质。Bcl-2蛋白家族及其家族成员共同构成一个异常复杂的相互作用网络,调控细胞凋亡。其调节细胞凋亡的机制可能于Bcl-2蛋白家族与线粒体、Bcl-2蛋白的相互作用、细胞内Ca2+;及氧自由基有关。②p53基因对防止细胞增生和保持DNA受损基因组的完整性有重要作用。p53调控细胞凋亡包括对外源性凋亡途径的调节和内源性凋亡途径的调控,p53基因究竟通过什么样的途径调控细胞凋亡?不同的实验因为不同的遗传学背景和微环境而不同。③目前主要有3种实验方法来研究p53基因对细胞凋亡的调控作用:第1种方法是通过识别p53激活的基因组的DNA断片,或者是启动所包含的依赖p53激活的因子。第2种方法是系统地识别受p53基因分别调控的基因组(或DNA组)。第3种方法是识别受p53调控的基本凋亡因子。结论:大量的凋亡因子是依赖p53激活调节细胞凋亡的,细胞凋亡中Bcl-2蛋白家族、p53基因的调控机制的分析,充分发挥细胞凋亡对机体有利的方面,对治疗各种癌症和心血管疾病具有广阔的应用前景。

OBJECTIVE： Cell apoptosis is the capacity of cells to undergo programmed cell death, which is controlled by a series of genasin the ontogeny course. Among most cell types, original cancer albumen Bclo2 protein family and p53 gene are important factors to the apoptosis, connecting and interacting with each other in the apoptosis to regulate the apoptosis. In this review, to control and regulate the mechanism of Bcl-2 protein family and p53 gene on cell apoptosis. DATA SOURCES： A computer-based online search of related articles between 1995 and 2006 was conducted in Pubmed and Springer link by inputting the key words of ＂apoptosis, Bcl-2 protein family, p53^n, and the language was limited to English. Meanwhile, relevant Chinese articles between 1995 and 2006 ware also searched in China Journal Full-text Database （CJFD） and Wanfang database with the key words in Chinese. Basis for Cell Apoptosis and Clinical Application was manually looked for. STUDY SELECTION： Data were checked in the first trial with the inclusion criteria of below： ① Relationship between Bcl-2 and apoptosis. ②Relationship between p53 and apoptosis. ③Researches on cell apoptosis and gene regulation. ④Study on the mechanism of Bcl-2 family and p53 gene regulation in cell apoptosis. DATA EXTRACTION： A total of 70 relevant literatures ware collected. Chinese literatures were full texts, and most of foreign literatures were full texts, and others were abstracts. Thirty-two enrolled relevant articles were about the relationship and mechanism of Bcl-2 protein family, p53 gene and apoptosis as well as gene regulation of cell apoptosis. DATA SYNTHESIS： ① Bcl-2 protein family is the most common protein in researches on relevant gene of cell apoptosis, including two kinds of protein with contradictory effects on cell apoptosis. Bclo2 protein family and its family members construct a complicated interacting net to regulate cell apoptosis. The regulative mechanism on cell apoptosis might be related to Bcl-2 protein family and mitochondria, the reciprocity among Bcl-2 protein family and Ca^2＋ and oxygen free radical. ②p53 gene is important for cell proliferation and impairing DNA geno groups, p53 gene regulation on cell apoptosis includes regulation on exogenous apoptosis and endogenous apoptosis. How do p53 gene regulate cell apoptosis on earth？ Different experiments get different results due to different genetics background and microenvironment. ③ At present, there are three main methods in research on the regulation of p53 gene in the apoptosis. First, to distinguish DNA fragment and activate the genes activated by p53. Secondly,to distinguish genome or DNA groups activated by p53. Thirdly, to distinguish the basic apoptosis gene activated by p53. CONCLUSION： Many apoptosis gena are activated by p53. I focus on the control and regulative mechanism of Bcl-2 protein family and p53 gene to the apoptosis, and it may open up new vistas of research for cancer and angiocardiopethy.