肿瘤坏死因子-α诱导肝损伤中细胞凋亡的多种机制剖析。
Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury.
作者信息
Ding Wen-Xing, Yin Xiao-Ming
机构信息
Department of Pathology, University of Pittsburgh, School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
出版信息
J Cell Mol Med. 2004 Oct-Dec;8(4):445-54. doi: 10.1111/j.1582-4934.2004.tb00469.x.
Abstract
Tumor necrosis factor (TNF)-alpha-induced hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure. TNF-alpha exerts a variety of effects that are mediated mainly by TNF-receptor 1 (TNF-R1) in cell death. The activation of TNF-R1 leads to 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 events, resulting in apoptosis. This article reviews the recent progress in the molecular mechanisms of TNF-alpha-induced apoptosis in hepatocytes, and discusses how these molecular findings are shaping our understanding of the pathogenesis of liver diseases and our strategy to develop novel therapeutics.
摘要
肿瘤坏死因子（TNF）-α诱导的肝细胞凋亡与多种肝脏疾病有关，包括病毒性肝炎、酒精性肝炎、缺血/再灌注肝损伤和暴发性肝衰竭。TNF-α发挥多种作用，主要通过肿瘤坏死因子受体1（TNF-R1）介导细胞死亡。TNF-R1的激活导致多种凋亡途径的激活，包括促死亡Bcl-2家族蛋白的激活、活性氧、C-Jun氨基末端激酶、组织蛋白酶B、酸性鞘磷脂酶和中性鞘磷脂酶。这些途径紧密相连，主要作用于线粒体，线粒体释放凋亡因子及其他事件，导致细胞凋亡。本文综述了TNF-α诱导肝细胞凋亡分子机制的最新进展，并讨论了这些分子研究结果如何塑造我们对肝脏疾病发病机制的理解以及开发新型治疗方法的策略。
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