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中国生物工程杂志

China Biotechnology
China Biotechnology  2015, Vol. 35 Issue (10): 72-77    DOI: 10.13523/j.cb.20151011
    
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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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 wordsGlutathione      Oxidative stress      Signaling pathways      Apoptosis      Liver diseases     
Received: 14 April 2015      Published: 25 October 2015
ZTFLH:  Q257  
Cite this article:

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.

URL:

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

[1] Richie J P, Skowronski L, Abraham P, et al. Blood glutathione concentrations in a large-scale human study. Clin Chem, 1996,42(01):64-70.
[2] 王璇,张鹏,李冬民. 氢过氧化物及谷胱甘肽过氧化物酶在肿瘤发生过程中的作用. 国外医学(医学地理分册),2015,36(01):71-74. Wang X, Zhang P, Li D M. The function of hydroperoxides and glutathione peroxidases in the process of tumorigenesis. Foreign Medical Science Section of Medgeography ,2015,36(01):71-74.
[3] 赵雪梅.谷胱甘肽在铅中毒治疗中的辅助作用. 工业卫生与职业病,2015,41(01):52-54. Zhao X M. The supporting role of glutathione in the therapy of lead poisoning . Ind Hlth & Occup Dis,2015,41(01):52-54.
[4] 赵凤. 砷-谷胱甘肽复合物的降解及含砷化合物对谷胱甘肽清除自由基的影响.天津:天津大学,2012. Zhao F. Study on the degradation of arsenic-glutathione and influence of arsenicals for free radical scavenging by glutathione.Tianjin: Tianjin University,2012.
[5] 李民,冯银刚,高杨,等. 谷氧还蛋白系统及其对细胞氧化还原态势的调控. 生物物理学报, 2007,23(5): 343-350. Li M, Feng Y G, Gao Y, et al. Glutaredoxin system and its regulation to the cytosolic thiol-redox status . Acta Biophysica Sinica,2007,23(5):343-350.
[6] 张春晶,于海涛,邹朝霞,等. 谷氧还蛋白的生物学活性及其与人类疾病的关系. 生命的化学. 2006,26 (02): 163-165. Zhang C J, Yu H T, Zhou C X, et al. Relationship glutaredoxin biological activity and its relationship with human diseases . Chemistry of Life,2006,26(02):163-165.
[7] Shelton M D, Distler A M, Kern T S, et al. Glutaredoxin regulates autocrine and paracrine proinflammatory responses in retinal glial (Müller) cells. 2009,284(08):4760-4766.
[8] Biswas S, Chida A S, Rahman I. Redox modifications of protein-thiols: Emerging roles in cell signaling.Biochem Pharmacol, 2006, 71(05):551-564.
[9] Brar S S, Grigg C, Wilson K S , et al. Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol Cancer Ther, 2004, 3(09):1049-1060.
[10] Qanungo S, Starke D W, Pai H V, et al. Glutathione supplementation potentiates hypoxic apoptosis by S-glutathionylation of p65-NFκB. Journal of Biological Chemistry, 2007, 282(25):18427-18436.
[11] Matsumaru K, Ji C, Kaplowitz N. Mechanisms for sensitization to TNF-induced apoptosis by acute glutathione depletion in murine hepatocytes.Hepatology , 2003,37 (6):1425-1434.
[12] Brown G C, Borutaite V. Regulation of apoptosis by the redox state of cytochrome C. Biochim Biophys Acta,2008,1777(7-8):877-881.
[13] 程莉. 拉米夫定联合还原型谷胱甘肽治疗重型乙肝血清MMP-13、TNF-α、TGF-β1变化及疗效. 海南医学院学报,2015,21(03):319-322. Cheng L. Effect of lamivudine with reduced glutathione therapy on serum MMP-13, TNF-α, TGF-β1 of patients with severe hepatitis B . Journal of Hainan Medical University,2015,21(03):319-322.
[14] 张雷,戴一菲. 阿德福韦酯联合还原型谷胱甘肽对代偿期乙型肝炎后肝硬化患者肝功能和炎性因子水平的影响及其疗效分析. 海南医学院学报,2015,21(02):194-196. Zhang L , Dai Y F. Effect of adefovir dipivoxil combined with reduced glutathione on liver function and inflammatory factor leves of patients with compensated posthepatitic cirrhosis. Journal of Hainan Medical University , 2015,21(02):194-196.
[15] 文秀玉,席宏杰. NF-κB信号转导与肝脏疾病关系的研究进展. 胃肠病学和肝病学杂志,2014,23(02):127-130. Wen X Y, Xi H J. Relationship between NF-κB pathway and liver disease . Chin J Gastroenterol Hepatol,2014,23(02):127-130.
[16] 张勇,鲍红光,尹加林,等. N-乙酰半胱氨酸对大鼠肝脏缺血再灌注损伤NF-κ B和ICAM-1表达的影响. 现代生物医学进展,2010,10(23):4454-4457. Zhang Y, Bao H G, Yin J L, et al. Effect of N-acetylcysteine on expression of NF-κ B and ICAM-1 in rats with hepatic ischemia/reperfusion injury. Progress in Modern Biomedicine,2010,10(23):4454-4457.
[17] 张伟. NF-κB、氧化应激在酒精性脂肪肝发病机制中的作用及水飞蓟素干预研究.合肥:安徽医科大学,2012. Zhang W. The Effects of NF-κB and oxidative stress in the pathogenesis of alcoholic fatty liver and its suppression by silymarin.Hefei:Anhui Medical University,2012.
[18] Reynaert N L. Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta. Proc Natl Acad Sci USA, 2006,103(35):13086-13091.
[19] Nish T, Shimizu N, Hiramoto M, et al. Spatial redox regulation of a critical cysteine residue of NF-kappaB in vivo. J Biol Chem, 2002,277 (46):44548-44556.
[20] 李燕,万汝根. N-乙酰半胱氨酸对心衰兔氧化应激和核因子NF-κB的干预研究. 中国生化药物杂志,2015,35(02):55-58. Li Y, Wan R G. Effect of N-acetylcsteine on oxidative stress and NF-κB in heart failure rabbits and its mechanism . Chinese Journal of Biochemical Pharmaceutics,2015,35(02):55-58.
[21] Glineur C, Davioud-Charvet E, Vandenbunder B. The conserved redox-sensitive cysteine residue of the DNA-binding region in the c-Rel protein is involved in the regulation of the phosphorylation of the protein. Biochem J, 2000, 352 (Pt 2):583-591.
[22] Lou H, Kaplowitz N. Glutathione depletion down-regulates tumor necrosis factor alpha-induced NF-kappaB activity via IkappaB kinase-dependent and -independent mechanisms. J Biol Chem, 2007, 282 (40):29470-29481.
[23] 王新,陈凤玲. 线粒体的功能及检测方法. 医学综述,2011,17(1):12-15. Wang X, Chen F L. Mitochondrial function and detection methods. Medical Recapitulate,2011,17(1):12-15.
[24] 郑天胜,李翔. 线粒体凋亡通路的研究进展. 医学综述,2013,19(18):3282-3285. Zheng T S, Li X. Research progress in mitochondrial apoptosis pathway. Medical Recapitulate,2013,19(18):3282-3285.
[25] Cande C, Vahsen N, Garrido C, et al. Apoptosis-inducing factor (AIF): caspase-independent after all. Cell Death Differ, 2004,11 (6):591-595.
[26] Zoratti M, Szabo I, De Marechi U. Mitochondrial permeability transitions:how many doors to the house?. Biochim Biophys Acta, 2005,1706(1/2):40-52.
[27] Youle R J, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol, 2008,9 (1):47-59.
[28] 吴伟,徐蔚. 线粒体通透性转换孔结构和功能的研究进展. 医学信息,2011,24(3):1753-1754. Wu W, Xu W. Progress in the studies of the structure and function of mitochondria permeaability transition pore. Medical Information,2011,24(3): 1753-1754.
[29] Halestrap A P,Clarke S J, Khaliulin I, et al.The role of mitochondria in protection of the heart by preconditioning .Biochim Biophys Acta, 2007,1767(8):1007-1031.
[30] Baines C P, Kaiser R A, Sheiko T, et al. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol, 2007,9(5): 550-555.
[31] Nakagawa T, Shimizu S, Watanabe T, et al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature, 2005,434 (7033):652-658.
[32] Lu C, Armstrong J S. Role of calcium and cyclophilin D in the regulation of mitochondrial permeabilization induced by glutathione depletion. Biochem Biophys Res Commun, 2007,363 (3):572-577.

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