摘要
细胞凋亡是指生理性或者病理性因素触发细胞内预存的死亡程序,内质网应激(ERS)在细胞凋亡过程中发挥着重要作用。氧化应激、Ca2+稳态失衡及缺氧等可引起蛋白质在内质网内的折叠受到抑制,促使未折叠蛋白聚集,引起ERS,激活未折叠蛋白反应,若此反应持续存在,则可诱发细胞凋亡。ERS包括PERK、IRE1、ATF6三条经典的信号通路,由PERK介导的信号通路能快速减少蛋白质的合成,减轻内质网的负荷; IRE1和ATF6介导的信号通路能增加内质网分子伴侣蛋白的合成,增加内质网蛋白的折叠、转运和降解的能力,减轻内质网的负荷。ERS参与了心肌缺血再灌注损伤、衰老、骨质疏松、肝硬化、肿瘤等疾病的发生发展,针对ERS进行干预有望成为治疗凋亡相关疾病的重要靶点。
引文
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