Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury.
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.
Aleksunes
Lauren M
LM
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092, USA.
Goedken
Michael
M
Manautou
José E
JE
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
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human