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TNF-α诱导肝细胞凋亡机制的回顾与展望
http://www.100md.com 李晶媛, 李树臣, 杨维良
凋亡;线粒体;Bcl-2家族蛋白;TNF-a;活性氧;肝损伤李晶媛,李树臣,杨维良.TNF-a诱导肝细胞凋亡机制的回顾与展望. 世界华人消化杂志2007;15(6)606-6112YinXM,DingWX.Deathreceptoractivation-inducedhepatocyte
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     李晶媛, 李树臣, 哈尔滨医科大学附属第二临床医学院感染科 黑龙江省哈尔滨市150086

    杨维良,
哈尔滨医科大学附属第二临床医学院普外三科 黑龙江省哈尔滨市150086

    通讯作者:
李树臣, 150086, 黑龙江省哈尔滨市学府路246号, 哈尔滨医科大学附属第二医院感染科. shuchenli@yahoo.com.cn

    电话:
0451-86671309 传真: 0451-86605614

    收稿日期:
2006-11-09 接受日期: 2006-12-27

    Review and prospect on mechanisms of tumor necrosis factor-α-induced apoptosis in liver injury

    Jing-Yuan Li, Shu-Chen Li, Wei-Liang Yang

    Jing-Yuan Li, Shu-Chen Li,Department of Infectious Diseases, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilonjiang Province, China

    Wei-Liang Yang,
the Third Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilonjiang Province, China

    Correspondence to:
Shu-Chen Li, Department of Infectious Diseases, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin 150086, Heilongjiang Province, China. shuchenli@yahoo.com.cn

    Received:
2006-11-09 Accepted:2006-12-27

    

    Abstract
Hepatocyte apoptosis induced by tumor necrosis factor-a (TNF-a) is implicated in a variety of liver diseases. TNF-a exerts various effects in cell apoptosis, which are mainly mediated by TNF-receptor 1 (TNF-R1). The responses of TNF-R1 resulted in the activation of multiple apoptotic pathways involving the activation of the pro-death Bcl-2 family proteins, reactive oxygen species, c-Jun NH2-terminal kinase, cathepsin B, acidic sphingomyelinase and neutral sphingomyelinase. These pathways are closely interlinked, and mainly act on mitochondria, which release the apoptogenic factors and other substances, leading to cell apoptosis. In this article, we reviewed the mechanisms of TNF-a-induced apoptosis of liver cells.

    Key Words: Apoptosis; Mitochondria; Bcl-2 family protein; Tumor necrosis factor-α; Reactive oxygen species; Liver injuryLi JY, Li SC, Yang WL. Review and prospect on mechanisms of tumor necrosis factor-a-induced apoptosis in liver injury. Shijie Huaren Xiaohua Zazhi 2007;15(6):606-611

    摘要

    在多种肝脏疾病中都涉及到TNF-a诱导的肝细胞凋亡. TNF-a在细胞凋亡过程中发挥多种效应, 主要由TNF-R1介导. TNF-R1的激活导致了多种凋亡途径的激活, 包括促凋亡的Bcl-2家族蛋白、活性氧、c-Jun NH2-末端激酶、组织蛋白酶B、酸性鞘磷脂酶及中性鞘磷脂酶. 这些途径密切相关并主要作用于线粒体, 线粒体释放致凋亡因子及其他物质, 导致细胞凋亡.

    关键词: 凋亡; 线粒体; Bcl-2家族蛋白; TNF-a;活性氧; 肝损伤

    李晶媛, 李树臣, 杨维良. TNF-a诱导肝细胞凋亡机制的回顾与展望. 世界华人消化杂志 2007;15(6):606-611

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    3 Wang Y, Singh R, Lefkowitch JH, Rigoli RM, Czaja MJ. Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway. J Biol Chem 2006; 281: 15258-15267 PubMed

    4 Muto Y, Nouri-Aria KT, Meager A, Alexander GJ, Eddleston AL, Williams R. Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure ......

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