title: Hepatitis B virus alters the antioxidant system in transgenic mice and sensitizes hepatocytes to Fas signaling.
abstract: Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the precise pathogenetic mechanisms linking HBV infection and HCC remain uncertain. It has been reported that decreased antioxidant enzyme activities are associated with severe liver injury and hepatocarcinogenesis in mouse models. It is unclear if HBV can interfere with the activities of antioxidant enzymes. We established a HBV transgenic mouse line, which spontaneously developed HCC at 2 years of age. We studied the activities of the antioxidant enzymes in the liver of the HBV transgenic mice. Our results showed that the antioxidant enzymes glutathione peroxidase and superoxide dismutase 2 were down-regulated in HBV transgenic mice and correlated with JNK activation. HBV enhanced the Fas-mediated activation of caspase 6, caspase 8 and JNK without enhancing the activation of caspase 3 and hepatocellular apoptosis. As a proper redox balance is important for maintaining cellular homeostasis, these effects of HBV on the host antioxidant system and Fas-signaling may play an important role in HBV-induced hepatocarcinogenesis.
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Na
authors.forename: Jing-hsiung James
authors.initials: JH
authors.lastname: Ou
authors.forename: Lynn
authors.initials: L
authors.lastname: Pulliam
authors.forename: T S Benedict
authors.initials: TS
authors.lastname: Yen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D053178:Caspase 6 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006515:Hepatitis B virus / Q000472:pathogenicity*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism / Q000821:virology; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D053178:Caspase 6; D053181:Caspase 8; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019014:fas Receptor; D000099156:Superoxide Dismutase 2; C491899:Fas protein, mouse; C505516:Casp6 protein, mouse; C505526:Casp8 protein, mouse