有哪些信誉好的足球投注网站activation of cd40 with platelet derived cd154 promotes reactive oxygen species dependent death of human hepatocytes during hypoxia and reoxygenation与血小板激活cd40派生cd154促进活性氧相关死亡的人类肝细胞在缺氧和再氧化.pdfVIP
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activation of cd40 with platelet derived cd154 promotes reactive oxygen species dependent death of human hepatocytes during hypoxia and reoxygenation与血小板激活cd40派生cd154促进活性氧相关死亡的人类肝细胞在缺氧和再氧化
Activation of CD40 with Platelet Derived CD154
Promotes Reactive Oxygen Species Dependent Death of
Human Hepatocytes during Hypoxia and Reoxygenation
Ricky H. Bhogal*, Christopher J. Weston, Stuart M. Curbishley, David H. Adams, Simon C. Afford
Centre for Liver Research, School of Infection and Immunity, Institute of Biomedical Research, The Medical School, The University of Birmingham, Edgbaston, Birmingham,
United Kingdom
Abstract
Background: Hypoxia and hypoxia-reoxygenation (H-R) are pathogenic factors in many liver diseases that lead to
hepatocyte death as a result of reactive oxygen species (ROS) accumulation. The tumor necrosis factor super-family member
CD154 can also induce hepatocyte apoptosis via activation of its receptor CD40 and induction of autocrine/paracrine Fas
Ligand/CD178 but the relationship between CD40 activation, ROS generation and apoptosis is poorly understood. We
hypothesised that CD40 activation and ROS accumulation act synergistically to drive human hepatocyte apoptosis.
Methods: Human hepatocytes were isolated from liver tissue and exposed to an in vitro model of hypoxia and H-R in the
presence or absence of CD154 and/or various inhibitors. Hepatocyte ROS production, apoptosis and necrosis were
determined by labelling cells with 29,7 9-dichlorofluorescin, Annexin-V and 7-AAD respectively in a three-colour reporter flow
cytometry assay.
Results: Exposure of human hepatocytes to recombinant CD154 or platelet-derived soluble CD154 augments ROS
accumulation during H-R resulting in NADPH oxidase-dependent apoptosis and necrosis. The inhibition of c-Jun N-terminal
Kinase and p38 attenuated CD154-mediated apoptosis but not necrosis.
Conclusions: CD154-mediated apoptosis of hepatocytes involves R
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