摘要
谷胱甘肽(GSH)是细胞内主要的抗氧剂和氧化还原、细胞信号调节器,它能还原过氧化氢、清除活性氧(ROS)和含氮自由基使细胞免受氧化应激损伤。不管细胞内是否存在ROS氧化细胞蛋白,谷胱甘肽均能诱导氧化还原反应发生转变,进一步使信号传导功能及转录因子分子功能发生改变。大量实验表明,ROS和GSH在多条细胞信号调节通路中发挥着重要作用。主要阐述了Fas、TNF-α和NF-κB信号通路及线粒体凋亡途径及GSH在这些通路中的作用。尤其是线粒体GSH耗竭能诱导线粒体内ROS显著增加,从而损害细胞生物能量和诱导线粒体通透性转换孔开启。根据线粒体损害程度,NF-κB信号通路可被抑制,肝细胞也可能经历不同的死亡模式(凋亡或坏死)并对刺激细胞死亡信号(如TNF-α)也更敏感。这些过程涉及许多肝脏疾病的发病机理。
Glutathione （GSH） is a major antioxidant, as well as redox and cell signaling regulator. GSH Protects cells from oxidative injury by reducing H2O2, scavenging reactive oxygen and nitrogen radicals. In addition, GSH-induced redox shift with or without ROS subjects some cellular proteins to varied forms of oxidation, further altering the function of signal transduction and transcription factor molecules. A lot of experiments showed that ROS and GSH play important roles in modulating multiple signaling pathways. Fas and TNF-a signaling, NF-KB and mitochondrial apoptotic pathways are focused on. Notably, the depletion of mitochondrial GSH induces increased mitochondria] ROS exposure which impairs bioenergetics and promotes mitochondrial permeability transition pore opening which is critical for cell death. Depending on the extent of mitochondrial damage, NF-κB inhibited and hepatocytes may either undergo different modes of cell death （apoptosis or necrosis ） or be sensitized to cell death stimuli （i. e. TNF-α ）. These processes have been implicated in the pathogenesis of many liver diseases.
出处
《中国生物工程杂志》
CAS
CSCD
北大核心
2015年第10期72-77,共6页
China Biotechnology
基金
国家"十二五"科技支撑计划课题资助项目(2011BAI04B01)
关键词
谷胱甘肽
肝脏疾病
信号通路
氧化应激
凋亡
Glutathione Liver diseases Signaling pathways Oxidative stress Apoptosis
