title: Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury.
abstract: OBJECTIVE
  To investigate the expression and activity of NAD(P)H quinone oxidoreductase 1 (NQO1) in human liver specimens obtained from patients with liver damage due to acetaminophen (APAP) overdose or primary biliary cirrhosis (PBC).
  
  
  METHODS
  NQO1 activity was determined in cytosol from normal, APAP and PBC liver specimens. Western blot and immunohistochemical staining were used to determine patterns of NQO1 expression using a specific antibody against NQO1.
  
  
  RESULTS
  NQO1 protein was very low in normal human livers. In both APAP and PBC livers, there was strong induction of NQO1 protein levels on Western blot. Correspondingly, significant up-regulation of enzyme activity (16- and 22-fold, P< 0.05) was also observed in APAP and PBC livers, respectively. Immunohistochemical analysis highlighted injury-specific patterns of NQO1 staining in both APAP and PBC livers.
  
  
  CONCLUSIONS
  These data demonstrate that NQO1 protein and activity are markedly induced in human livers during both APAP overdose and PBC. Up-regulation of this cytoprotective enzyme may represent an adaptive stress response to limit further disease progression by detoxifying reactive species.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
authors.forename: Michael
authors.initials: M
authors.lastname: Goedken
authors.forename: José E
authors.initials: JE
authors.lastname: Manautou
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000150:complications; D008107:Liver Diseases / Q000201:enzymology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human