内质网应激与软骨细胞凋亡

Endoplasmic reticulum stress and apoptosis of chondrocytes

背景:细胞可以通过未折叠蛋白反应,对自己产生一种保护作用,但如果出现内质网应激的强度很大,或者持续的时间过久,均可能致使细胞的凋亡。故内质网应激与许多疾病有着千丝万缕的关系。目的:在近年来发表的文献基础上对内质网应激与疾病的关系,以及其可能的作用机制进行综述。方法:应用计算机由第一作者在Pub Med数据库和中国知网数据库,以"Endoplasmic reticulum stress;apoptosis"为英文检索词,以"内质网应激;凋亡"为中文检索词,在1999年1月至2016年10月间共检索到4 883篇相关文献,排除重复研究,共59篇文献符合纳入标准。结果与结论:目前认为内质网在蛋白质合成和折叠过程起着至关重要的作用,内质网既是蛋白质合成与折叠的场地,又可以保持钙离子的动态平衡,而且也是脂类和固醇合成的重要场所。外界因素的变化可以致使内质网的功能发生紊乱而引发内质网应激,然后出现未折叠蛋白反应。未折叠或错误折叠蛋白在内质网蓄积引发内质网应激,导致细胞内稳态失衡,其主要后果是细胞凋亡,从而对机体组织和器官造成损伤。

BACKGROUND:Although the unfolded protein response is a cellular protective response to the endoplasmic reticulum stress,hight-intensity or persistent endoplasmic reticulum stress can still induce cell apoptosis.Therefore,the endoplasmic reticulum stress is closely related to the occurrence and development of various diseases.OBJECTIVE:To overview the relationship between the endoplasmic reticulum stress and diseases,and the possible mechanisms.METHODS:The first author retrieved PubMed and CNKI databases by computer for the literature published from January1999to October2016using the keywords of“endoplasmic reticulum stress,apoptosis”in English and Chinese,respectively.Initially4883relevant articles were searched.After exclusion of the repetitive studies finally59eligible articles were enrolled in accordance with the inclusion criteria.RESULTS AND CONCLUSION:The endoplasmic reticulum has been shown to play a crucial role in protein synthesis and folding process,as well as in maintenance of Ca2+homeostasis,and synthesis of lipids and sterols places.Endoplasmic reticulum dysfunction caused by genetic or environmental damage leads to endoplasmic reticulum stress,followed by the unfolded protein response.Unfolded or misfolded proteins accumulate in the endoplasmic reticulum and trigger the endoplasmic reticulum stress,resulting in cellular homeostasis imbalance.The main consequence is apoptosis,thereby causing damage to tissues and organs.