title: Apoptosis and Bcl-2 expression in the livers of patients with steatohepatitis.
abstract: OBJECTIVE
  Apoptosis may play a role in the pathogenesis of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH). In this study, we investigated the modulation of apoptosis-related liver proteins in steatohepatitis.
  
  
  METHODS
  Hepatocyte apoptosis was evaluated by the TUNEL assay in liver tissue of 12 patients with NASH, 12 with ASH and in histologically normal controls. In addition, caspase-3 processing was evaluated by immunoblot analysis. Expression of death receptors, Bcl-2 family members, and NF-kappaB inhibitor (IkappaB) were determined by western blot. Liver biopsies were also graded for inflammation and fibrosis.
  
  
  RESULTS
  Apoptotic hepatocytes were markedly increased in NASH (P<0.05) and ASH (P<0.001) as compared to controls. Active caspase-3 was also elevated in steatohepatitis (P<0.01), coinciding with upregulation of pro-apoptotic Bax (P<0.001). Further, production of tumour necrosis factor-receptor 1 was increased up to 4-fold (P<0.05). Degradation of IkappaB increased >70% in steatohepatitis (P<0.001). Notably, Bcl-2 was also strongly expressed (>100-fold; P<0.001). These data were significantly correlated with relative degrees of portal and lobular inflammation.
  
  
  CONCLUSIONS
  The results show that liver injury in NASH and ASH is associated with apoptosis and NF-kappaB activation. Anti-apoptotic Bcl-2 is strongly expressed, probably reflecting an adaptive response to obesity or alcohol-related stress.
authors.affiliation: Centro de Patogénese Molecular, Faculty of Pharmacy, University of Lisbon and Department of Gastroenterology, Hospital of Santa Maria, Lisbon, Portugal.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Ramalho
authors.forename: Helena
authors.initials: H
authors.lastname: Cortez-Pinto
authors.forename: Rui E
authors.initials: RE
authors.lastname: Castro
authors.forename: Susana
authors.initials: S
authors.lastname: Solá
authors.forename: Adília
authors.initials: A
authors.lastname: Costa
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Moura
authors.forename: Maria E
authors.initials: ME
authors.lastname: Camilo
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
mesh_terms: D000328:Adult; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D005235:Fatty Liver, Alcoholic / Q000378:metabolism / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases