谷胱甘肽在肝脏疾病相关信号通路中的作用及研究进展

doi:10.13523/j.cb.20151011

中国生物工程杂志

2015, Vol. 35

Issue (10): 72-77 DOI: 10.13523/j.cb.20151011

综述

谷胱甘肽在肝脏疾病相关信号通路中的作用及研究进展

胡燕珍¹, 卫军营², 罗光明¹

1. 江西中医药大学药学院南昌 330004;
2. 中国中医科学院中药研究所北京 100700

Research on Glutathione-related Signaling Pathway in Liver Diseases

HU Yan-zhen¹, WEI Jun-ying², LUO Guang-ming¹

1. College of Pharmacy Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;
2. Institute of Chinese Medica, China Academy of Traditional Chinese Medical Science, Beijing 100700, China

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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。

关键词： 谷胱甘肽; 信号通路; 凋亡; 肝脏疾病; 氧化应激

Abstract:

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-κB and mitochondrial apoptotic pathways are focused on. Notably, the depletion of mitochondrial GSH induces increased mitochondrial 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.

Key words: Glutathione Oxidative stress Signaling pathways Apoptosis Liver diseases

收稿日期: 2015-04-14 出版日期: 2015-10-25

ZTFLH:

Q257

基金资助:

国家"十二五"科技支撑计划课题资助项目(2011BAI04B01)

通讯作者: 罗光明 E-mail: 992830182@qq.com

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引用本文:

胡燕珍, 卫军营, 罗光明. 谷胱甘肽在肝脏疾病相关信号通路中的作用及研究进展[J]. 中国生物工程杂志, 2015, 35(10): 72-77.

HU Yan-zhen, WEI Jun-ying, LUO Guang-ming. Research on Glutathione-related Signaling Pathway in Liver Diseases. China Biotechnology, 2015, 35(10): 72-77.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20151011 或 https://manu60.magtech.com.cn/biotech/CN/Y2015/V35/I10/72

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