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Gene Review

Nox1  -  NADPH oxidase 1

Mus musculus

Synonyms: GP91 phox homolog, GP91-2, MOX1, NOH-1, NOH1, ...
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Disease relevance of Nox1

  • Finally, Nox1 partially restores superoxide production in neutrophils differentiating ex vivo from gp91(phox)-deficient CD34(+) peripheral blood-derived stem cells derived from patients with X-linked chronic granulomatous disease [1].
  • Transduction with retrovirus encoding Nox1 restored activation and differentiation-dependent superoxide production in gp91(phox)-deficient PLB-985 cells, indicating close functional similarities to the phagocyte oxidase (phox) [1].
  • Both inducible nitric oxide synthase and NADPH oxidase contribute to the control of virulent phase I Coxiella burnetii infections [2].
  • Abrupt reoxygenation of microvascular endothelial cells after hypoxia activates ERK1/2 and JNK1, leading to NADPH oxidase-dependent oxidant production [3].
  • NOXO1, which was upregulated in all three treatment groups, positively regulates the expression of a subunit of NADPH oxidase (NOX1), a major source of reactive oxygen species, and may play an important role in the pathogenesis of COPD [4].
  • NADPH oxidase inhibitors blocked the production of lyso-PS in vitro, and accordingly, its generation in vivo by activated, murine neutrophils during zymosan-induced peritonitis was absent in mice lacking a functional NADPH oxidase (gp91phox-/-) [5].

Psychiatry related information on Nox1


High impact information on Nox1

  • Therefore, NOX2 plays a critical role in conferring DCs the ability to function as specialized phagocytes adapted to process antigens rather than kill pathogens [8].
  • The NADPH oxidase NOX2 is recruited to the DC's early phagosomes and mediates the sustained production of low levels of reactive oxygen species, causing active and maintained alkalinization of the phagosomal lumen [8].
  • NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells [8].
  • Here we show that COS-7 cells transfected with four NADPH oxidase components, but lacking H+ channels, produce O2- in the presence of Zn2+ concentrations that inhibit O2- production in neutrophils and eosinophils [9].
  • The enzyme NADPH oxidase in phagocytes is important in the body's defence against microbes: it produces superoxide anions (O2-, precursors to bactericidal reactive oxygen species) [9].

Chemical compound and disease context of Nox1


Biological context of Nox1

  • A large number of genes, including many related to cell cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in Nox1-expressing cells, and more than 60% of these returned to normal levels on coexpression of catalase [14].
  • This study explores the role of reactive oxygen species (ROS) in regulating cell growth and transformation by Nox1 [14].
  • Moreover, both RANKL-mediated ROS production and osteoclast differentiation were completely blocked in precursors depleted of Nox1 activity by RNA interference or by expressing a dominant-negative mutant of Rac1 [15].
  • The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation [16].
  • These studies demonstrate a significant functional homology (cofactor-dependent and activation-regulated superoxide production) between Nox1 and its closest homologue, gp91(phox), suggesting that targeted up-regulation of Nox1 expression in phagocytic cells could provide a novel approach in the molecular treatment of chronic granulomatous disease [1].

Anatomical context of Nox1

  • In situ hybridization in mouse colon revealed high Nox1 expression within the lower two-thirds of colon crypts, where epithelial cells undergo proliferation and differentiation [1].
  • Furthermore, coexpression of cytosolic components, p47(phox) and p67(phox), augments Nox1 activity in reconstituted K562 cells [1].
  • We previously reported the cloning of Nox1 (NADPH oxidase1), a homolog of gp91phox, its expression in colon and vascular smooth muscle, and its oncogenic properties when overexpressed [Suh et al. (1999). Nature 401, 79-82] [17].
  • Aortas of Tg(p22smc) mice had increased p22(phox) and Nox1 protein levels and produced more superoxide and H(2)O(2) [18].
  • In neuroprogenitor, hypothalamic, and lymphoid cells, ERK1/2 activation is fully controlled by the NADPH oxidase-dependent ROS production [19].

Associations of Nox1 with chemical compounds

  • H(2)O(2) concentration increased approximately 10-fold in Nox1-expressing cells, compared with <2-fold increase in O(2)(-) [14].
  • We studied the expression and function of a recently described source of ROS, NAD(P)H oxidase 1 or Nox1, which has been associated with cell proliferation [1].
  • In unstimulated VSMCs, phosphorothioate antisense oligonucleotides against Nox4 down-regulated mRNA expression of the subunit by 65% and attenuated superoxide production by 41% without affecting Nox1 expression [20].
  • Vascular O2- and expression of the NADPH oxidase subunits p67phox and Nox1 were increased [21].
  • Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice [22].

Physical interactions of Nox1

  • First, we establish that 5-HT2B receptors and 1D adrenoceptors are functionally coupled to reactive oxygen species (ROS) synthesis through NADPH oxidase activation in 1C115-HT and 1C11NE cells [23].
  • Neuron-glia cultures from mice lacking a functional NADPH oxidase complex (PHOX-/-) were insensitive to substance P (10(-13)-10(-14) M) -induced loss of DA neuron function [24].

Enzymatic interactions of Nox1


Regulatory relationships of Nox1


Other interactions of Nox1

  • The highest levels of p41 transcript are detected in the colon and in other gastrointestinal tissues that express Nox1, the predominant gp91phox homologue in these tissues [31].
  • Furthermore, co-activation of JNK and Nox were sufficient to mimic the Rac mitogenic rescue [32].
  • Nox is playing with a full deck in vascular smooth muscle, a commentary on "Noxa1 is a central component of the smooth muscle NADPH oxidase in mice" [33].
  • Voglibose treatment decreased the myocardial expression of an NADPH oxidase subunit (p47phox) [34].
  • Proinflammatory mediators down-regulated Nox4 but did not affect Nox1 expression, so other factors must compensate to regulate superoxide production [20].

Analytical, diagnostic and therapeutic context of Nox1


  1. NAD(P)H oxidase 1, a product of differentiated colon epithelial cells, can partially replace glycoprotein 91phox in the regulated production of superoxide by phagocytes. Geiszt, M., Lekstrom, K., Brenner, S., Hewitt, S.M., Dana, R., Malech, H.L., Leto, T.L. J. Immunol. (2003) [Pubmed]
  2. Both inducible nitric oxide synthase and NADPH oxidase contribute to the control of virulent phase I Coxiella burnetii infections. Brennan, R.E., Russell, K., Zhang, G., Samuel, J.E. Infect. Immun. (2004) [Pubmed]
  3. Abrupt reoxygenation of microvascular endothelial cells after hypoxia activates ERK1/2 and JNK1, leading to NADPH oxidase-dependent oxidant production. Yu, G., Peng, T., Feng, Q., Tyml, K. Microcirculation (New York, N.Y. : 1994) (2007) [Pubmed]
  4. Gene expression profiling in lung tissues from mice exposed to cigarette smoke, lipopolysaccharide, or smoke plus lipopolysaccharide by inhalation. Meng, Q.R., Gideon, K.M., Harbo, S.J., Renne, R.A., Lee, M.K., Brys, A.M., Jones, R. Inhalation toxicology. (2006) [Pubmed]
  5. NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance of activated and dying neutrophils via G2A. Frasch, S.C., Berry, K.Z., Fernandez-Boyanapalli, R., Jin, H.S., Leslie, C., Henson, P.M., Murphy, R.C., Bratton, D.L. J. Biol. Chem. (2008) [Pubmed]
  6. NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Zhan, G., Serrano, F., Fenik, P., Hsu, R., Kong, L., Pratico, D., Klann, E., Veasey, S.C. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  7. virB-Mediated survival of Brucella abortus in mice and macrophages is independent of a functional inducible nitric oxide synthase or NADPH oxidase in macrophages. Sun, Y.H., den Hartigh, A.B., Santos, R.L., Adams, L.G., Tsolis, R.M. Infect. Immun. (2002) [Pubmed]
  8. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Savina, A., Jancic, C., Hugues, S., Guermonprez, P., Vargas, P., Moura, I.C., Lennon-Duménil, A.M., Seabra, M.C., Raposo, G., Amigorena, S. Cell (2006) [Pubmed]
  9. The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels. DeCoursey, T.E., Morgan, D., Cherny, V.V. Nature (2003) [Pubmed]
  10. O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Archer, S.L., Reeve, H.L., Michelakis, E., Puttagunta, L., Waite, R., Nelson, D.P., Dinauer, M.C., Weir, E.K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  11. Pressure overload-induced myocardial hypertrophy in mice does not require gp91phox. Maytin, M., Siwik, D.A., Ito, M., Xiao, L., Sawyer, D.B., Liao, R., Colucci, W.S. Circulation (2004) [Pubmed]
  12. Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Li, J., Baud, O., Vartanian, T., Volpe, J.J., Rosenberg, P.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Acetaminophen toxicity in mice lacking NADPH oxidase activity: role of peroxynitrite formation and mitochondrial oxidant stress. James, L.P., McCullough, S.S., Knight, T.R., Jaeschke, H., Hinson, J.A. Free Radic. Res. (2003) [Pubmed]
  14. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Arnold, R.S., Shi, J., Murad, E., Whalen, A.M., Sun, C.Q., Polavarapu, R., Parthasarathy, S., Petros, J.A., Lambeth, J.D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Lee, N.K., Choi, Y.G., Baik, J.Y., Han, S.Y., Jeong, D.W., Bae, Y.S., Kim, N., Lee, S.Y. Blood (2005) [Pubmed]
  16. The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation. Mitsushita, J., Lambeth, J.D., Kamata, T. Cancer Res. (2004) [Pubmed]
  17. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Cheng, G., Cao, Z., Xu, X., van Meir, E.G., Lambeth, J.D. Gene (2001) [Pubmed]
  18. Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice. Laude, K., Cai, H., Fink, B., Hoch, N., Weber, D.S., McCann, L., Kojda, G., Fukai, T., Schmidt, H.H., Dikalov, S., Ramasamy, S., Gamez, G., Griendling, K.K., Harrison, D.G. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  19. NADPH oxidase and extracellular regulated kinases 1/2 are targets of prion protein signaling in neuronal and nonneuronal cells. Schneider, B., Mutel, V., Pietri, M., Ermonval, M., Mouillet-Richard, S., Kellermann, O. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle. Ellmark, S.H., Dusting, G.J., Fui, M.N., Guzzo-Pernell, N., Drummond, G.R. Cardiovasc. Res. (2005) [Pubmed]
  21. NADPH oxidase accounts for enhanced superoxide production and impaired endothelium-dependent smooth muscle relaxation in BKbeta1-/- mice. Oelze, M., Warnholtz, A., Faulhaber, J., Wenzel, P., Kleschyov, A.L., Coldewey, M., Hink, U., Pongs, O., Fleming, I., Wassmann, S., Meinertz, T., Ehmke, H., Daiber, A., Münzel, T. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  22. Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Matsuno, K., Yamada, H., Iwata, K., Jin, D., Katsuyama, M., Matsuki, M., Takai, S., Yamanishi, K., Miyazaki, M., Matsubara, H., Yabe-Nishimura, C. Circulation (2005) [Pubmed]
  23. Reactive oxygen species-dependent TNF-alpha converting enzyme activation through stimulation of 5-HT2B and alpha1D autoreceptors in neuronal cells. Pietri, M., Schneider, B., Mouillet-Richard, S., Ermonval, M., Mutel, V., Launay, J.M., Kellermann, O. FASEB J. (2005) [Pubmed]
  24. Potent regulation of microglia-derived oxidative stress and dopaminergic neuron survival: substance P vs. dynorphin. Block, M.L., Li, G., Qin, L., Wu, X., Pei, Z., Wang, T., Wilson, B., Yang, J., Hong, J.S. FASEB J. (2006) [Pubmed]
  25. Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages. Kim, J.S., Kim, J.G., Jeon, C.Y., Won, H.Y., Moon, M.Y., Seo, J.Y., Kim, J.I., Kim, J., Lee, J.Y., Choi, S.Y., Park, J., Yoon Park, J.H., Ha, K.S., Kim, P.H., Park, J.B. Exp. Mol. Med. (2005) [Pubmed]
  26. Involvement of several protein kinases in the phosphorylation of p47-phox. Yamaguchi, M., Saeki, S., Yamane, H., Okamura, N., Ishibashi, S. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  27. Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1alpha and intracellular reactive oxygen species. Ateghang, B., Wartenberg, M., Gassmann, M., Sauer, H. J. Cell. Sci. (2006) [Pubmed]
  28. Developmental expression of NADPH phagocytic oxidase components in mouse embryos. Baehner, R.L., Millar-Groff, S., Bringas, P. Pediatr. Res. (1999) [Pubmed]
  29. Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS. Ding, H., Hashem, M., Triggle, C. Eur. J. Pharmacol. (2007) [Pubmed]
  30. NADPH-oxidase-driven oxygen radical production determines chondrocyte death and partly regulates metalloproteinase-mediated cartilage matrix degradation during interferon-gamma-stimulated immune complex arthritis. van Lent, P.L., Nabbe, K.C., Blom, A.B., Sloetjes, A., Holthuysen, A.E., Kolls, J., Van De Loo, F.A., Holland, S.M., Van Den Berg, W.B. Arthritis Res. Ther. (2005) [Pubmed]
  31. Proteins homologous to p47phox and p67phox support superoxide production by NAD(P)H oxidase 1 in colon epithelial cells. Geiszt, M., Lekstrom, K., Witta, J., Leto, T.L. J. Biol. Chem. (2003) [Pubmed]
  32. Abl tyrosine kinase regulates a Rac/JNK and a Rac/Nox pathway for DNA synthesis and Myc expression induced by growth factors. Boureux, A., Furstoss, O., Simon, V., Roche, S. J. Cell. Sci. (2005) [Pubmed]
  33. Nox is playing with a full deck in vascular smooth muscle, a commentary on "Noxa1 is a central component of the smooth muscle NADPH oxidase in mice". Lassègue, B., Griendling, K.K. Free Radic. Biol. Med. (2006) [Pubmed]
  34. Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice. Liao, Y., Takashima, S., Zhao, H., Asano, Y., Shintani, Y., Minamino, T., Kim, J., Fujita, M., Hori, M., Kitakaze, M. Cardiovasc. Res. (2006) [Pubmed]
  35. Expression and modulation of an NADPH oxidase in mammalian astrocytes. Abramov, A.Y., Jacobson, J., Wientjes, F., Hothersall, J., Canevari, L., Duchen, M.R. J. Neurosci. (2005) [Pubmed]
  36. Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+. Al-Mehdi, A.B., Zhao, G., Dodia, C., Tozawa, K., Costa, K., Muzykantov, V., Ross, C., Blecha, F., Dinauer, M., Fisher, A.B. Circ. Res. (1998) [Pubmed]
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