Bcl-2蛋白质家族调控细胞凋亡机制的研究进展

细胞凋亡是一种受基因调控的响应凋亡刺激的细胞程序性死亡方式.通过线粒体途径引发的凋亡主要由Bcl-2(B-cell lymphoma 2)蛋白质家族成员之间复杂的相互作用进行调控,然而科学界对其具体的相互作用模式一直存在争议.首先综述了近年来Bcl-2蛋白质家族成员之间相互作用的生物学机制,然后总结了细胞凋亡具有双稳性和该家族成员相互作用模式的数学模型,最后通过对目前流行的3种作用模式(即直接激活模式、间接激活模式、统一模式)进行数值模拟和分岔分析,认为统一模式是更合理的作用模式.以期能更好地理解病理细胞中可能存在的作用机制,从而为因凋亡异常引起的癌症、阿尔兹海默症等疾病的治疗和控制提供思路.

Research Progress on the Molecular Mechanism of Apoptosis Regulated by Bcl-2 Protein Families

Apoptosis is a form of programmed cell death controlled genetically in response to apoptotic stimuli or signals. Apoptosis induced by mitochondrial pathway is mainly regulated by the complex interplay between B-cell lymphoma 2( Bcl-2) protein family members. However,the detailed interplay mode remains debatable. In this paper,the molecular mechanism of the interaction between Bcl-2 family members was firstly reviewed. Secondly,the mathematical models were summarized about bistability emerged from apoptosis and the interaction mode of Bcl-2 family proteins,respectively. Finally,numerical simulations and bifurcation analysis were conducted for the three interplay modes( i. e.direct activation mode,indirect activation mode and unified mode) proposed by the biologists. The results are in favor of the unified mode as a most plausible interplay mode. The work is hoped to improve our understanding of the molecular mechanism in the pathological cells and to provide insights into the manipulation of the diseases caused by abnormal apoptosis,such as cancer and Alzheimer's disease.