The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Nqo1  -  NAD(P)H dehydrogenase, quinone 1

Rattus norvegicus

Synonyms: Azoreductase, DT-diaphorase, DTD, Menadione reductase, NAD(P)H:quinone oxidoreductase 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Nqo1

  • Quinone reductase promoter-chlor-amphenicol acetyltransferase fusion genes containing different lengths of the 5'-flanking region were transfected into rat and human hepatoma cells [1].
  • N,N,N', N'-Tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) and other cell-permeant metal chelators also effectively blocked DTDP-induced toxicity in neurons [2].
  • Expression of mammalian DT-diaphorase in Escherichia coli: purification and characterization of the expressed protein [3].
  • Rat liver NAD(P)H:quinone oxidoreductase cDNA was cloned and expressed in a eukaryotic cell expression plasmid containing a cytomegalovirus (CMV) promoter [4].
  • Nuclear localization of transfected NQO1 activity increased the cytotoxicity of MC over that produced by overexpression in the cytosol under both aerobic and hypoxic conditions, with greater cytotoxicity being produced under hypoxia [5].

High impact information on Nqo1

  • When microsomes were exposed to a concentration of deoxycholate which makes them permeable to macromolecules but does not disrupt the membrane, the detergent alone was sufficient to release four enzymes: nucleoside diphosphatase, esterase, beta-glucuronidase, and a portion of the DT-diaphorase [6].
  • Induction of phase 2 detoxication enzymes [e.g., glutathione transferases, epoxide hydrolase, NAD(P)H: quinone reductase, and glucuronosyltransferases] is a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity of electrophiles and reactive forms of oxygen [7].
  • The incorporation of dicoumarol, a potent inhibitor of DT-diaphorase, interfered with the protection provided by CoQ [8].
  • The interaction between DT-diaphorase and CoQ was also demonstrated in an isolated rat liver hepatocyte system [8].
  • DT-diaphorase was isolated and purified from rat liver cytosol, and its ability to reduce several CoQ homologs incorporated into large unilamellar vesicles was demonstrated [8].

Chemical compound and disease context of Nqo1

  • We have determined the effect of beta-naphthoflavone and the azo dye, sudan III, on the level of quinone reductase mRNA in a responsive rat hepatoma cell line [1].
  • Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity and selectivity in human lung and breast cancer cell lines [9].
  • It is concluded that, similar to glutathione, the oxidative stress limiting NQO is likely to contribute to the capacity of astroglial cells to protect dopaminergic neurons against L-Dopa, and, hence, may be considered as a potential target for the development of neuroprotective strategies for Parkinson's disease [10].
  • NADH consumption was accompanied by dicumarol-sensitive oxygen uptake both with the purified enzyme and with cytosol from human melanoma cells with high levels of DT-diaphorase activity [11].
  • The neuroprotective action of norepinephrine can be explained by (1) its ability to form complexes with Fe3+, (2) the uptake of Fe-norepinephrine complex via the norepinephrine transporter and (3) lack of toxicity of the Fe-norepinephrine complex even when DT-diaphorase is inhibited [12].

Biological context of Nqo1


Anatomical context of Nqo1

  • Treatment with EK significantly lowered PCNA index in ACF and reduced PGE2 content in the colonic mucosa, while EK elevated liver GST and QR activities [15].
  • The membrane-permeant oxidizing agent 2,2'-dithiodipyridine (DTDP) can induce Zn(2+) release from metalloproteins in cell-free systems [2].
  • The remaining 19 amino acid residues at the NH2 terminus were identical with those of the DT-diaphorase purified from rat liver cytosol [3].
  • NQO1, GST, and SULT1A1 activities in other brain regions including the cortex, cerebellum, and hippocampus were less sensitive to chronic E(2) treatment [16].
  • NQO1 was primarily localized in vascular elements and neurons and SULT1A1 primarily in neurons and neuropil of control and E(2)-treated rats [16].

Associations of Nqo1 with chemical compounds


Regulatory relationships of Nqo1


Other interactions of Nqo1


Analytical, diagnostic and therapeutic context of Nqo1


  1. Rat liver NAD(P)H: Quinone reductase. Regulation of quinone reductase gene expression by planar aromatic compounds and determination of the exon structure of the quinone reductase structural gene. Bayney, R.M., Morton, M.R., Favreau, L.V., Pickett, C.B. J. Biol. Chem. (1989) [Pubmed]
  2. Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release. Aizenman, E., Stout, A.K., Hartnett, K.A., Dineley, K.E., McLaughlin, B., Reynolds, I.J. J. Neurochem. (2000) [Pubmed]
  3. Expression of mammalian DT-diaphorase in Escherichia coli: purification and characterization of the expressed protein. Ma, Q., Wang, R., Yang, C.S., Lu, A.Y. Arch. Biochem. Biophys. (1990) [Pubmed]
  4. Rat liver NAD(P)H:quinone oxidoreductase: cDNA expression and site-directed mutagenesis. Forrest, G.L., Qian, J., Ma, J.X., Kaplan, W.D., Akman, S., Doroshow, J., Chen, S.A. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  5. Nuclear overexpression of NAD(P)H:quinone oxidoreductase 1 in Chinese hamster ovary cells increases the cytotoxicity of mitomycin C under aerobic and hypoxic conditions. Seow, H.A., Penketh, P.G., Belcourt, M.F., Tomasz, M., Rockwell, S., Sartorelli, A.C. J. Biol. Chem. (2004) [Pubmed]
  6. Enzyme and phospholipid asymmetry in liver microsomal membranes. Nilsson, O.S., Dallner, G. J. Cell Biol. (1977) [Pubmed]
  7. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Fahey, J.W., Zhang, Y., Talalay, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems. Beyer, R.E., Segura-Aguilar, J., Di Bernardo, S., Cavazzoni, M., Fato, R., Fiorentini, D., Galli, M.C., Setti, M., Landi, L., Lenaz, G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity and selectivity in human lung and breast cancer cell lines. Beall, H.D., Murphy, A.M., Siegel, D., Hargreaves, R.H., Butler, J., Ross, D. Mol. Pharmacol. (1995) [Pubmed]
  10. L-Dopa stimulates expression of the antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO) in cultured astroglial cells. van Muiswinkel, F.L., Riemers, F.M., Peters, G.J., LaFleur, M.V., Siegel, D., Jongenelen, C.A., Drukarch, B. Free Radic. Biol. Med. (2000) [Pubmed]
  11. Bioreductive activation of catechol estrogen-ortho-quinones: aromatization of the B ring in 4-hydroxyequilenin markedly alters quinoid formation and reactivity. Shen, L., Pisha, E., Huang, Z., Pezzuto, J.M., Krol, E., Alam, Z., van Breemen, R.B., Bolton, J.L. Carcinogenesis (1997) [Pubmed]
  12. Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra. Paris, I., Martinez-Alvarado, P., Perez-Pastene, C., Vieira, M.N., Olea-Azar, C., Raisman-Vozari, R., Cardenas, S., Graumann, R., Caviedes, P., Segura-Aguilar, J. J. Neurochem. (2005) [Pubmed]
  13. Rat liver NAD(P)H: quinone reductase nucleotide sequence analysis of a quinone reductase cDNA clone and prediction of the amino acid sequence of the corresponding protein. Bayney, R.M., Rodkey, J.A., Bennett, C.D., Lu, A.Y., Pickett, C.B. J. Biol. Chem. (1987) [Pubmed]
  14. Reaction of rat liver DT-diaphorase (NAD(P)H:quinone acceptor reductase) with 5'-[p-(fluorosulfonyl)benzoyl]-adenosine. Liu, X.F., Yuan, H., Haniu, M., Iyanagi, T., Shively, J.E., Chen, S.A. Mol. Pharmacol. (1989) [Pubmed]
  15. Extract of vinegar "Kurosu" from unpolished rice inhibits the development of colonic aberrant crypt foci induced by azoxymethane. Shimoji, Y., Sugie, S., Kohno, H., Tanaka, T., Nanda, K., Tamura, Y., Nishikawa, Y., Hayashi, R., Uenakai, K., Ohigashi, H. J. Exp. Clin. Cancer Res. (2003) [Pubmed]
  16. Phase II antioxidant enzyme activities in brain of male and female ACI rats treated chronically with estradiol. Stakhiv, T.M., Mesia-Vela, S., Kauffman, F.C. Brain Res. (2006) [Pubmed]
  17. The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol. Asher, G., Dym, O., Tsvetkov, P., Adler, J., Shaul, Y. Biochemistry (2006) [Pubmed]
  18. Characterization of selective induction and alteration of xenobiotic biotransforming enzymes by vanadium during diethylnitrosamine-induced chemical rat liver carcinogenesis. Bishayee, A., Roy, S., Chatterjee, M. Oncol. Res. (1999) [Pubmed]
  19. Coordinate polypeptide expression during hepatocarcinogenesis in male F-344 rats: comparison of the Solt-Farber and Reddy models. Wirth, P.J., Rao, M.S., Evarts, R.P. Cancer Res. (1987) [Pubmed]
  20. Dicoumarol-sensitive glucuronidation of benzo(a)pyrene metabolites in rat liver microsomes. Segura-Aguilar, J.E., Barreiro, V., Lind, C. Arch. Biochem. Biophys. (1986) [Pubmed]
  21. Comparison of hepatic carcinogen initiation-promotion systems. Leonard, T.B., Dent, J.G., Graichen, M.E., Lyght, O., Popp, J.A. Carcinogenesis (1982) [Pubmed]
  22. Effect of drugs and hormones on rat liver dimethylaminoazobenzene reductase activity. de-Araujo, P.S., de-Andrade-Silva, E., Raw, I. Braz. J. Med. Biol. Res. (1982) [Pubmed]
  23. Effects of the agrochemicals butachlor, pretilachlor and isoprothiolane on rat liver xenobiotic-metabolizing enzymes. Ishizuka, M., Iwata, H., Kazusaka, A., Hatakeyama, S., Fujita, S. Xenobiotica (1998) [Pubmed]
  24. Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats. Jahangir, T., Khan, T.H., Prasad, L., Sultana, S. Human & experimental toxicology. (2006) [Pubmed]
  25. 2-Methyl-1,4-naphthoquinone, vitamin K(3), decreases gap-junctional intercellular communication via activation of the epidermal growth factor receptor/extracellular signal-regulated kinase cascade. Klotz, L.O., Patak, P., Ale-Agha, N., Buchczyk, D.P., Abdelmohsen, K., Gerber, P.A., von Montfort, C., Sies, H. Cancer Res. (2002) [Pubmed]
  26. Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of DL-alpha-lipoic acid. Obrosova, I.G., Fathallah, L., Greene, D.A. Eur. J. Pharmacol. (2000) [Pubmed]
  27. Polychlorinated biphenyl-induced effects on metabolic enzymes, AP-1 binding, vitamin E, and oxidative stress in the rat liver. Twaroski, T.P., O'Brien, M.L., Larmonier, N., Glauert, H.P., Robertson, L.W. Toxicol. Appl. Pharmacol. (2001) [Pubmed]
  28. NAD(P)H:menadione oxidoreductase. Novel purification of enzyme cDNA and complete amino acid sequence, and gene regulation. Robertson, J.A., Chen, H.C., Nebert, D.W. J. Biol. Chem. (1986) [Pubmed]
  29. An unusual profile of musk xylene-induced drug-metabolizing enzymes in rat liver. Iwata, N., Minegishi, K., Suzuki, K., Ohno, Y., Igarashi, T., Satoh, T., Takahashi, A. Biochem. Pharmacol. (1993) [Pubmed]
WikiGenes - Universities