内质网应激与自噬及其交互作用影响内皮细胞凋亡
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摘要
内质网应激是普遍存在于真核细胞中的应激-防御机制。在内环境稳态遭到破坏的情况下,未折叠蛋白质反应的3条信号通路,分别通过增强蛋白质折叠能力、减少蛋白质生成和促进内质网相关蛋白质降解等途径缓解细胞内压力。同时,也通过多种分子信号机制调控细胞凋亡。自噬是一种生理性的降解机制。通过形成自噬泡并与溶酶体结合摄取并水解胞内受损细胞器和蛋白质等,清除代谢废物,维持细胞正常功能。自噬缺陷或过度激活均可导致细胞凋亡或非程序性死亡。自噬的程度和细胞内压力水平有关。内质网应激通过未折叠蛋白质反应和Ca~(2+)浓度变化及其相关分子信号调控自噬。自噬又可反馈性调节内质网应激反应,二者相互作用,在内皮细胞凋亡过程中发挥重要作用。未来内质网应激和自噬可作为药物靶点为内皮相关性疾病提供诊疗策略。
Endoplasmic reticulum stress is a prevalent stress-defense mechanism in eukaryotic cells. In the case of homeostasis disruption, the three signaling pathways of unfolded protein response are activated to relieve the intracellular pressure through enhancing protein folding, reducing protein production and promoting endoplasmic reticulum-related protein degradation. It regulates apoptosis through a variety of molecular signaling mechanisms. Autophagy is a physiological degradation mechanism that removes metabolic wastes and maintains normal cellular functions by forming autophagic vesicles and ingesting with lysosomes and hydrolyzing intracellular damaged organelles and proteins. Degeneration or over-activation of autophagy lead to apoptosis or non-programmed death and the degree of autophagy is related to the intracellular pressure level. Endoplasmic reticulum stress regulates autophagy through unfolded protein response and changes in Ca~(2+) concentration. Autophagy can also feedback the endoplasmic reticulum stress response and the interactions plays an important role in endothelial cell apoptosis. Future endoplasmic reticulum stress and autophagy can be used as drug targets to provide a diagnosis and treatment strategy for endothelial-related diseases.
Endoplasmic reticulum stress is a prevalent stress-defense mechanism in eukaryotic cells. In the case of homeostasis disruption, the three signaling pathways of unfolded protein response are activated to relieve the intracellular pressure through enhancing protein folding, reducing protein production and promoting endoplasmic reticulum-related protein degradation. It regulates apoptosis through a variety of molecular signaling mechanisms. Autophagy is a physiological degradation mechanism that removes metabolic wastes and maintains normal cellular functions by forming autophagic vesicles and ingesting with lysosomes and hydrolyzing intracellular damaged organelles and proteins. Degeneration or over-activation of autophagy lead to apoptosis or non-programmed death and the degree of autophagy is related to the intracellular pressure level. Endoplasmic reticulum stress regulates autophagy through unfolded protein response and changes in Ca~(2+) concentration. Autophagy can also feedback the endoplasmic reticulum stress response and the interactions plays an important role in endothelial cell apoptosis. Future endoplasmic reticulum stress and autophagy can be used as drug targets to provide a diagnosis and treatment strategy for endothelial-related diseases.
引文
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