内质网应激中Caspase-12的核心作用

The Core Role of Caspase-12 in Endoplasmic Reticulum Stress

内质网(ER)是细胞中一个重要的细胞器,主要功能是脂质的合成、储存以及蛋白质的折叠、加工等。因此,严格调控和维持内质网稳态是至关重要的。在缺氧、Ca^(2+)稳态发生紊乱或者在机体需求和蛋白质折叠装置能力不平衡等情况下都会引起内质网应激(ERS),此时内质网会启动了细胞的一个适应性反应,这种反应被称之为未折叠蛋白反应(UPR)。结果,定位于内质网的分子伴侣被诱导,蛋白质的合成会减缓,与此同时蛋白质的降解系统也会启动。如果内质网应激不能被缓解,细胞凋亡将随之发生。本综述分析了由内质网应激所引起的未折叠蛋白反应信号通道,以及Caspase-12在内质网凋亡途径中的核心作用。这为细胞凋亡的研究提供了一个新的角度,对肿瘤等疾病的治疗提供了一定的理论依据。

Endoplasmic reticulum（ER） is an important organelle in cells,whose main functions are the synthesis and storage of lipid,as well as the folding and processing of protein.Therefore,strict regulation and maintenance of endoplasmic reticulum is crucial.Under the condition of hypoxic,the disorder of Ca^（2＋）homeostasis or imbalance between the demand and capacity of the protein folding devices,endoplasmic reticulum stress（ERS） would appear.At this time,the endoplasmic reticulum would initiate an adaptive response of cells,which was called the unfolded protein response（UPR）.As a result,the molecular chaperone of ER-localized was induced,then protein synthesis was slowed down,and degradation system of protein would activate.If the ERS could not be mitigated,apoptosis would ensue.In this paper,we summarized the URP signaling pathway triggered by the activation of endoplasmic reticulun and elaborates the central role of the Caspase-12 in initiating apoptosis.This provided a new perspective for apoptosis research and laid a theoretical foundation for the treatment of cancer and other diseases.