title: Ethanol potentiates hepatitis B virus replication through oxidative stress-dependent and -independent transcriptional activation.
abstract: Excessive alcohol intake accelerates disease progression in chronic hepatitis B virus (HBV) infection, but the mechanisms by which ethanol worsens the prognosis of chronic hepatitis B (CHB) are not fully understood. The aim of this study was to investigate whether HBV replication is augmented by alcohol or alcohol-induced cytochrome p450 2E1 (CYP2E1), and if so, whether oxidative stress is involved in the process. Ethanol treatment promoted HBV replication in HepAD38 cells that permit the conditional viral replication. Luciferase reporter assays confirmed that HBV core, preS1 and preS2/S promoter activities were augmented by ethanol. Ethanol did not induce oxidative stress in HepAD38 cells with minimal expression of CYP2E1. However, over-expression of CYP2E1 induced oxidative stress and amplified transcriptional activation of HBV by ethanol. Antioxidant glutathione treatment attenuated CYP2E1-mediated augmentation of HBV replication in ethanol-treated cells. In conclusion, ethanol enhances transcriptional activity of HBV promoters in human hepatoma cells in an oxidative stress-independent manner; and CYP2E1-mediated oxidative stress potentiates the ethanol-induced transactivation of HBV.
authors.affiliation: Department of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Min
authors.forename: Nam Young
authors.initials: NY
authors.lastname: Kim
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jang
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Sang Hyup
authors.initials: SH
authors.lastname: Lee
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1