title: [Hepatitis C virus core protein upregulates the transcription of PCK1 through FOXO1/PGC-1alpha pathway].
abstract: OBJECTIVE
  We analyzed the effect of the stable expressed Hepatitis C virus core protein on PCK1 mRNA expression level and the molecular mechanisms involved in Huh7-lunet cells.
  
  
  METHODS
  A retroviral vector mediated mammalian cell expression cell line of the HCV core protein was constructed. The mRNA and protein levels of PCK1, FOXO1 and PGC-1alpha were analyzed by Real-time PCR and luciferase assay in Huh7-lunet-core cells.
  
  
  RESULTS
  HCV CORE upregulated the mRNA levels of PCK1 significantly. Both the mRNA and protein levels of FOXO1 were not affected in Huh7-lunet-core cells, whereas a decreased phosphorylation status of FOXO1 was exhibited. Moreover, activation of FOXO1 by HCV CORE was detected. Further, the mRNA level of PGC-1alpha was found to be significantly elevated in Huh7-lunet-core cells.
  
  
  CONCLUSIONS
  Our results revealed for the first time that HCV core protein expression-mediated FOXO1 activation and the increased PGC-1alpha leaded to the elevation of PCK1 at the mRNA level, which suggesting the immoderate gluconeogenesis in HCV-infected hepatocytes. Our findings contributed to the understanding of the molecular mechanisms of HCV-related insulin resistance and provided potential new clues for the prevention and therapy of diabetes.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Science, Nanjing Medical University, Nanjing 210093, China. chenjizheng2005@sina.com.cn
authors.forename: Jizheng
authors.initials: J
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: Xu
mesh_terms: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000502:physiology*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D014758:Viral Core Proteins; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)