ChemInform Abstract: NAD(P)H:quinone Oxidoreductase 1 (NQO1): Chemoprotection, Bioactivation, Gene Regulation and Genetic Polymorphisms

Department of Pharmaceutical Sciences, School of Pharmacy and Cancer Center, Box C-238, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA.
Chemico-Biological Interactions (Impact Factor: 2.58). 05/2001; 129(1-2):77-97. DOI: 10.1016/S0009-2797(00)00199-X
Source: PubMed


NAD(P)H:quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase that is involved in chemoprotection and can also bioactivate certain antitumor quinones. This review focuses on detoxification reactions catalyzed by NQO1 and its role in antioxidant defense via the generation of antioxidant forms of ubiquinone and vitamin E. Bioactivation reactions catalyzed by NQO1 are also summarized and the development of new antitumor agents for the therapy of solid tumors with marked NQO1 content is reviewed. NQO1 gene regulation and the role of the antioxidant response element and the xenobiotic response element in transcriptional regulation is summarized. An overview of genetic polymorphisms in NQO1 is presented and biological significance for chemoprotection, cancer susceptibility and antitumor drug action is discussed.

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    • "PARP-1 activation is also known as one of the important pathogenic mechanisms in cisplatin-induced toxicity (Mukhopadhyay et al., 2011; Shino et al., 2003). The cytosolic antioxidant flavoprotein NADH:quinone oxidoreductase 1 (NQO1) uses NADH as an electron donor to catalyze the reduction of substrates, which consequently increases intracellular NAD þ levels (Gaikwad et al., 2001; Ross et al., 2000). NQO1 has also been implicated in anti-inflammatory processes, scavenging of superoxide anion radicals, and stabilization of p53 and other tumor suppressor proteins (Jones et al., 2007; Moscovitz et al., 2012; Pazdro and Burgess, 2012). "
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    • "The enzyme catalyses the NADH or NADPH-dependent reduction of a variety of organic compounds, including quinones [78] [79] [80] [81] [82]. Its cellular role is not wholly clear, but it seems likely that NQO1 participates in the detoxification of xenobiotic compounds and also in the cycling of quinones in the cell [75]. Since it catalyses the two electron reduction of quinones directly to the corresponding quinols, it avoids the production of potentially damaging semiquinones [83]. "
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