國家衛生研究院 NHRI:Item 3990099045/3160
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    题名: Acute expression of hepatitis C core protein in adult mouse liver: Mitochondrial stress and apoptosis
    作者: Chang, ML;Chen, JC;Chang, MY;Yeh, CT;Lin, WP;Liang, CK;Huang, SF;Dang, KN;Chiu, CT;Lin, DY
    贡献者: Division of Molecular and Genomic Medicine
    摘要: Objective. In infection with hepatitis C virus (HCV), spontaneous clearance of the virus occurs in 30-40% of cases. By contrast, in chronic infection, this is rare. The basis for viral clearance in acute disease is unknown. Whereas cellular immune responses have been studied in detail, few data exist on the role of viral structural proteins, such as the core protein. The purpose of this study was to investigate the effects of core produced de novo within adult mouse hepatocytes by using a new transgenic mouse line in which expression of HCV core is regulated by tetracycline (tet-off). Material and methods. In this work, transgenic mice with conditional HCV core were created, to study the acute expression of HCV core protein in the context of the mature liver. The subcellular distribution of the core, hepatocellular oxidative stress and apoptosis were monitored. Results. Core protein is readily detectable and strongly associated with cytoplasmic lipid vesicles, endoplasmic reticulum and mitochondria. Mitochondrial oxidative stress was evidenced by a reduction in thioredoxin-2 (trx2). Concurrently, caspase-3 activity and TUNEL increased and, over time, the level of core protein in the liver declined. Conclusions. Mice that are conditionally transgenic for HCV core protein, which is readily detected and morphologically associated with steatosis in individual hepatocytes, were developed. Acute expression of core protein causes mitochondrial stress, as demonstrated by a reduction in trx2 and in the apoptosis of core-positive hepatocytes. We speculate that these events could be involved in the clearance of virus during acute hepatitis C, by both reducing the burden of virus in the liver and effectively priming the immune response.
    关键词: Gastroenterology & Hepatology
    日期: 2008
    關聯: Scandinavian Journal of Gastroenterology. 2008;43(6):747-755.
    Link to: http://dx.doi.org/10.1080/00365520701875987
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0036-5521&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000257028100015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=45749131483
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