title: Hepatitis B virus X protein sensitizes HL-7702 cells to oxidative stress-induced apoptosis through modulation of the mitochondrial permeability transition pore.
abstract: Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and cancer. Among the pathogenic factors of HBV, HBV X protein (HBx) is attracting increased attention. Although it is documented that HBx is a multifunctional regulator that modulates cell inflammation and apoptosis, the exact mechanism remains controversial. In the present study, we explored the effect of HBx on oxidative stress-induced apoptosis in normal liver cell line, HL-7702. Our results showed that the existence of HBx affected mitochon-drial biogenesis by modulating the opening of the mitochondrial permeability transition pore (MPTP). Notably, this phenomenon was associated with a pronounced translocation of Bax from the cytosol to the mitochon-dria during the period of exposure to oxidative stress with a release of cytochrome c and activation of cleaved caspase-3 and PARP. Moreover, MPTP blockage with cyclosporin A prevented the translocation of Bax, and inhibited oxidative stress-induced apoptotic killing in the HBx-expressing HL-7702 cells. Our findings suggest that HBx exhibits pro-apoptotic effects upon normal liver cells following exposure to oxidative stress by modulating the MPTP gateway.
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Graduate School, Fujian Medical University, Fujian 350001, P.R. China.
authors.forename: De-En
authors.initials: DE
authors.lastname: Cai
authors.affiliation: Graduate School, Fujian Medical University, Fujian 350001, P.R. China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China.
authors.forename: Bi-Yun
authors.initials: BY
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China.
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China.
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051028:bcl-2-Associated X Protein; C057628:hepatitis B virus X protein; D006861:Hydrogen Peroxide