EGCG通过mTOR通路拮抗低氧诱导的PC12细胞的凋亡与自噬  

EGCG antagonizes hypoxia-induced autophagy and apoptosis in PC12 cells by m TOR regulation

作　　者：曹锦霞 王浩[1] 王红卫[1] 游咏[1] 

机构地区：[1]南华大学附属第一医院,湖南衡阳421000

出　　处：《中国病理生理杂志》2014年第11期1960-1966,共7页Chinese Journal of Pathophysiology

基　　金：湖南省科技厅面上项目(No.2013FJ3133)

摘　　要：目的:氯化钴(cobalt chloride,Co Cl2)诱导的低氧具有神经毒性,可以诱导神经细胞的凋亡和自噬。茶多酚活性成分表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)具有一定的抗细胞凋亡和自噬的作用,但作用机理尚未完全阐明。近年来有研究报道,雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)通路参与了多种神经功能的调节,如神经细胞的分化成熟、抗氧化应激等。为此,我们用Co Cl2诱导低氧引起细胞的凋亡与自噬,从m TOR通路探讨EGCG拮抗Co Cl2诱导低氧引起细胞凋亡与自噬的作用机制。方法:研究使用Western blotting方法测定Co Cl2以及EGCG处理后m TOR和自噬蛋白beclin-1的表达,使用ELISA法检测细胞caspase-3表达,CCK-8检测细胞活力,免疫荧光法观察LC-3在胞核内的表达。结果:Co Cl2诱导低氧引起了细胞凋亡与自噬,而EGCG通过m TOR通路拮抗了Co Cl2诱导低氧引起的细胞凋亡与自噬,阻断m TOR通路则逆转了EGCG对神经细胞的保护作用。结论:EGCG通过m TOR通路拮抗了Co Cl2诱导的低氧引起的PC12细胞的凋亡与自噬。AIM： Hypoxia（ evoked by Co Cl2）-induced apoptosis and autophagy are emerging as crucial events in the etiopathology of many neurodegenerative diseases. Epigallocatechin gallate（ EGCG） is the active ingredient in tea polyphenols with abilities of anti-apoptosis and anti-autophagy,but the mechanism has not been fully elucidated. In recent years,studies have reported that the mammalian target of rapamycin（ m TOR） involved in the regulation of a variety of neurological like differentiation and maturation of nerve cells,anti-oxidative stress,etc. Therefore,we investigate that whether EGCG protects PC12 from hypoxia-induced apoptosis and autophagy by enhancing m TOR expression. METHODS： The expression of m TOR and beclin-1 were detected by Western blotting. The expression of caspase-3 was measured by ELISA.The cell viability was detected by CCK-8 assay. The LC-3 expression in nucelus was observed by immunofluorescence. RESULTS： Hypoxia induced apoptosis and autophagy in PC12 cells. EGCG antagonized hypoxia-induced apoptosis and autophagy by enhancing m TOR expression. Blocking the pathway of m TOR reversed the protective effect of EGCG on PC12 cells. CONCLUSION： EGCG antagonizes hypoxia-induced autophagy and apoptosis in PC12 cells by controlling m TOR regulation.

关 键 词：表没食子儿茶素没食子酸酯 雷帕霉素靶蛋白 低氧 氯化钴 凋亡 自噬 

分 类 号：R363[医药卫生—病理学]