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. 2006 Mar 28;12(12):1937-40.
doi: 10.3748/wjg.v12.i12.1937.

Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury

Lauren M Aleksunes  1 , Michael Goedken, José E Manautou
Affiliations

Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury

Lauren M Aleksunes et al. World J Gastroenterol. .

Abstract

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.

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Figures

Figure 1
Figure 1
NQO1 protein (A) and activity (B) in cytosolic fractions from normal, APAP and PBC human liver specimens. The data are presented as nmol reduced DCPIP/min/mg protein ± SE (n = 3-5, aP < 0.05 vs normal liver specimens).
Figure 2
Figure 2
Immunoperoxidase staining of NQO1 in normal (A, B), APAP (C, D), and PBC (E, F) human liver specimens as well as in PBC hyperplastic biliary epithelium (G, H).
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