title: Activation of AMPK/MnSOD signaling mediates anti-apoptotic effect of hepatitis B virus in hepatoma cells.
abstract: OBJECTIVE
  To investigate the anti-apoptotic capability of the hepatitis B virus (HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.
  
  
  METHODS
  Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase (MnSOD), AMP-activated protein kinase (AMPK) and hepatitis B virus X protein (HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes.
  
  
  RESULTS
  HBV markedly protected the hepatoma cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of MnSOD expression and activity was found in HepG2.215 cells. Moreover, AMPK activation contributed to the up-regulation of MnSOD. HBx protein was identified to induce the expression of AMPK and MnSOD.
  
  
  CONCLUSIONS
  Our results suggest that HBV suppresses mitochondrial superoxide level and exerts an anti-apoptotic effect by activating AMPK/MnSOD signaling pathway, which may provide a novel pharmacological strategy to prevent HCC.
authors.affiliation: Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China.
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Hong
authors.affiliation: Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China.
authors.forename: Cai-Qi
authors.initials: CQ
authors.lastname: Ma
authors.affiliation: Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China.
authors.forename: Han-Yan
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Lei Li, Hong-Hai Hong, Shi-Ping Chen, Han-Yan Liu, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China.
authors.forename: Ya-Chao
authors.initials: YC
authors.lastname: Yao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology / Q000821:virology; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology / Q000821:virology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Apoptosis; Hepatitis B virus; Manganese superoxide dismutase; Reactive oxygen species