title: A role for MHBst167/HBx in hepatitis B virus-induced renal tubular cell apoptosis.
abstract: BACKGROUND
  The pathogenesis of hepatitis B virus (HBV)-associated glomerulonephritis (HBVGN) is generally believed to be immune complex deposition. However, the presence of HBV-DNA and -RNA in HBVGN renal tissues suggested a direct virally induced injury. We previously showed that nuclear factor kappaB (NF-kappaB) was activated in HBVGN renal tissues, especially in tubular cells. We therefore investigated the role of NF-kappaB in tubular epithelial cells with HBV infection.
  
  
  METHODS
  Nuclear translocation of NF-kappaB and alpha subunit of NF-kappaB inhibitor (IkappaBalpha) phosphorylation were assessed by immunodetection following transfection of HK-2 cells with mhbs(t167) and/or hbx. Electrophoretic mobility shift assays (EMSA) and dual luciferase reporter assays (DLR) were used to further examine NF-kappaB activation following transfection. Hochest 33258 and NF-kappaB/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) double staining were used to detect apoptosis and the correlation between NF-kappaB activation and apoptosis. Protein kinase C (PKC) assay and ERK phosphorylation were assayed for a possible mechanism of NF-kappaB activation.
  
  
  RESULTS
  Cells transfected with mhbs(t167) and/or hbx increased NF-kappaB nuclear translocation, phosphor-IkappaBalpha, kappaB-DNA binding activity, kappaB-dependent transcription and apoptotic index compared to controls (P < 0.05). The nuclear distribution of NF-kappaB strongly correlated to cellular apoptosis. PKC activity and phosphor-ERK were also increased (P < 0.05) during the NF-kappaB activation process. However, all above parameters were diminished after pyrrolidine dithiocarbamate (PDTC)-incubation, a NF-kappaB inhibitor (P < 0.05).
  
  
  CONCLUSIONS
  MHBs(t167)/HBx-induced NF-kappaB activation via the PKC/ERK pathway in renal tubular cells undergoing apoptosis may be involved in virally induced pathogenesis.
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, 15 Changle Western Road, 710032, Xi'an, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Min
authors.forename: Jianrong
authors.initials: J
authors.lastname: Lu
authors.forename: Fanfan
authors.initials: F
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Shuangping
authors.initials: S
authors.lastname: Guo
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology / Q000821:virology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D016328:NF-kappa B / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D016328:NF-kappa B; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C114312:middle envelope protein, Hepatitis B virus; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases