内质网应激反应分子机理研究进展

Molecular Mechanism on Endoplasmic Reticulum Stress Responses

内质网应激是导致心脑组织缺血梗塞、神经退行性疾病等发生的重要环节 .目前发现同型半胱氨酸、氧化应激、钙代谢紊乱等都能引起内质网应激级联反应 ,表现为蛋白质合成暂停、内质网应激蛋白表达和细胞凋亡等 .这些表现包括在未折叠蛋白反应 (UPR)、整合应激反应 (ISR)和内质网相关性死亡 (ERAD)三个相互关联的动态过程中 ,每一过程的分子机理现已逐步被揭示 .作为细胞保护性应对机制的内质网应激体系一旦遭到破坏 ,细胞将不能合成应有的蛋白质 ,亦不能发挥正常的生理功能 ,甚至会出现细胞凋亡 .

Endoplasmic reticulum (ER) stress has been recognized as one of most important contributors to diabetes mellitus and neurodegenerative disorders. Homocysteine, oxidative stress and calcium metabolism disturbance were proved to induce endoplasmic reticulum stress cascade processes, including inhibition of protein synthesis initiation, expression of endoplasmic reticulum stress protein, and/or endoplasmic reticulum related apoptosis. Each of those dynamic processes can be biochemical discerned and dissected into unfolded protein response (UPR), integrated stress response (ISR), and/or endoplasmic reticulum associated death (ERAD) respectively. The cells will be eliminated by apoptosis via ERAD, once while their ER stress responses unfavorably go beyond UPR and ISR processes. A comprehensive understanding of the impact of the ER stress pathway within those suffering cells on their pathological process might be conducive to provide a new target for the prevention and treatment of those diseases.