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World J Gastroenterol. Mar 28, 2006; 12(12): 1937-1940
Published online Mar 28, 2006. doi: 10.3748/wjg.v12.i12.1937
Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury
Lauren M Aleksunes, Michael Goedken, José E Manautou
Lauren M Aleksunes, José E Manautou, University of Connecticut, Department of Pharmaceutical Sciences, Unit 3092, Storrs, CT, United States
Michael Goedken, University of Connecticut, Department of Pathobiology, Unit 3089, Storrs, CT, United States
Correspondence to: Dr. José E. Manautou, Toxicology Program, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092, United States. jose.manautou@uconn.edu
Telephone: +1-860-4863852 Fax: +1-860-4865792
Received: August 19, 2005
Revised: August 22, 2005
Accepted: August 31, 2005
Published online: March 28, 2006

AIM: 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.

CONCLUSION: 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.

Keywords: NQO1, Quinone oxidoreductase, Acetaminophen, APAP, Primary biliary cirrhosis, PBC, Nrf2, Diaphorase