细胞焦亡的研究进展

Research advances of pyroptosis

细胞焦亡是一种由炎性体激活促炎性半胱氨酸蛋白酶所引发的程序性细胞死亡。此类蛋白酶属于半胱氨酸天冬氨酸蛋白水解酶家族,家族中参与细胞焦亡的蛋白酶包括促炎性半胱氨酸蛋白酶1、4、5、11,这些蛋白可对Gasdermin D蛋白的N端特异性切割,进而激活其成孔活性,致使质膜破裂。细胞焦亡的典型特征除了质膜破裂外还伴随着促炎因子和细胞内容物的释放,其中包括IL-1β、IL-18和内源性危险性信号蛋白HMGB-1。目前,由caspase-1介导了经典途径中的细胞焦亡,而通过caspase-4、5、11直接识别脂多糖(LPS)所引发的细胞焦亡被定义为非经典途径。相关研究表明,在由细菌、病毒所引起的传染性疾病如志贺氏菌病、艾滋病等中存在细胞焦亡,此外,在非传染性疾病如引发动脉粥样硬化等的疾病中也发现有细胞焦亡的存在。本文主要对细胞焦亡的特征、机制和相关疾病研究进行综述,目的在于对进一步深入研究细胞焦亡的机制奠定基础。

Pyroptosis is a programmed cell death,which is caused by inflammasomes activated pro-inflammatory cysteine-containing proteases that belong to the family of cysteine-containing aspartate proteases(caspases).The proteases involved in pyroptosis including pro-inflammatory cysteine-containing proteases 1,4,5,11(caspase-1,4,5,11)could induce the specific cleave of N-ter-minus of the Gasdermin D protein,activation of poreforming activity and plasma membrane rupture.Pyroptosis could release the pro-inflammatory cytokines and entocytes,including IL-1β,IL-18,and endogenous risk signaling protein HMGB-1.At present,the canonical pathway of pyroptosis is considered to be mediated by caspase-1,However,the casapse-4,5 and 11 recognized Lipopolysaccharide(LPS)could induce the non-canonical pathway of pyroptosis.Data from recent investigations have shown that the pyroptosis was induced in several bacterial or virus diseases,such as Shigellosis and AIDS.In addition,research confirmed that pyroptosis was also induced in no-infectious diseases(atherosclerosis).This paper reviews the researches of characteristics,mechanism and relative diseases.This paper would provide foundation of pyroptosis for further investigations.