Abstract
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). 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. 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. 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.
MeSH Terms
Acetaminophen/adverse effects
Adolescent
Adult
Analgesics, Non-Narcotic/adverse effects
Female
Gene Expression Regulation, Enzymologic
Humans
Immunohistochemistry
Liver/enzymology,pathology
Liver Cirrhosis, Biliary/complications
Liver Diseases/enzymology,etiology
Male
Middle Aged
NAD(P)H Dehydrogenase (Quinone)/genetics
Up-Regulation
Chemicals
Analgesics, Non-Narcotic
Acetaminophen
NAD(P)H Dehydrogenase (Quinone)
NQO1 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Aleksunes Lauren M
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092, USA.
Goedken Michael
Manautou José E
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