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Gene Review

Nox4  -  NADPH oxidase 4

Rattus norvegicus

Synonyms: KOX-1, Kidney oxidase-1, Kidney superoxide-producing NADPH oxidase, Kox
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Disease relevance of Nox4


High impact information on Nox4

  • We investigated the role of the NAD(P)H oxidase Nox4 in generation of reactive oxygen species (ROS), hypertrophy, and fibronectin expression in a rat model of type 1 diabetes induced by streptozotocin [1].
  • Phosphorothioated antisense (AS) or sense oligonucleotides for Nox4 were administered for 2 weeks with an osmotic minipump 72 h after streptozotocin treatment [1].
  • Nox4 protein expression was increased in diabetic kidney cortex compared with non-diabetic controls and was down-regulated in AS-treated animals [1].
  • In conclusion, Nox4 and Nox1 are upregulated by the renin-angiotensin system [3].
  • Nox1 and Nox4 were expressed in the vascular smooth muscle cell (VSMC) line A7r5 and aortas and kidneys of rats [3].

Chemical compound and disease context of Nox4


Biological context of Nox4


Anatomical context of Nox4


Associations of Nox4 with chemical compounds


Other interactions of Nox4

  • Dominant negative Rac1 (N17Rac1) as well as AS Nox4 inhibited ROS generation in response to ANG II and AA, whereas constitutively active Rac1 stimulated ROS formation [4].
  • The aortic expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox1, Nox2, Nox4, and p22phox) was higher in SHR compared with WKY [10].

Analytical, diagnostic and therapeutic context of Nox4


  1. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. Gorin, Y., Block, K., Hernandez, J., Bhandari, B., Wagner, B., Barnes, J.L., Abboud, H.E. J. Biol. Chem. (2005) [Pubmed]
  2. Increased NADPH-oxidase activity and Nox4 expression during chronic hypertension is associated with enhanced cerebral vasodilatation to NADPH in vivo. Paravicini, T.M., Chrissobolis, S., Drummond, G.R., Sobey, C.G. Stroke (2004) [Pubmed]
  3. Upregulation of the vascular NAD(P)H-oxidase isoforms Nox1 and Nox4 by the renin-angiotensin system in vitro and in vivo. Wingler, K., Wünsch, S., Kreutz, R., Rothermund, L., Paul, M., Schmidt, H.H. Free Radic. Biol. Med. (2001) [Pubmed]
  4. Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells. Gorin, Y., Ricono, J.M., Kim, N.H., Bhandari, B., Choudhury, G.G., Abboud, H.E. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  5. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Ago, T., Kitazono, T., Ooboshi, H., Iyama, T., Han, Y.H., Takada, J., Wakisaka, M., Ibayashi, S., Utsumi, H., Iida, M. Circulation (2004) [Pubmed]
  6. H2O2 activates Nox4 through PLA2-dependent arachidonic acid production in adult cardiac fibroblasts. Colston, J.T., de la Rosa, S.D., Strader, J.R., Anderson, M.A., Freeman, G.L. FEBS Lett. (2005) [Pubmed]
  7. Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Hilenski, L.L., Clempus, R.E., Quinn, M.T., Lambeth, J.D., Griendling, K.K. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  8. NAD(P)H oxidases in rat basilar arterial endothelial cells. Ago, T., Kitazono, T., Kuroda, J., Kumai, Y., Kamouchi, M., Ooboshi, H., Wakisaka, M., Kawahara, T., Rokutan, K., Ibayashi, S., Iida, M. Stroke (2005) [Pubmed]
  9. Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats. Nishiyama, A., Yao, L., Nagai, Y., Miyata, K., Yoshizumi, M., Kagami, S., Kondo, S., Kiyomoto, H., Shokoji, T., Kimura, S., Kohno, M., Abe, Y. Hypertension (2004) [Pubmed]
  10. Reversal of endothelial nitric oxide synthase uncoupling and up-regulation of endothelial nitric oxide synthase expression lowers blood pressure in hypertensive rats. Li, H., Witte, K., August, M., Brausch, I., Gödtel-Armbrust, U., Habermeier, A., Closs, E.I., Oelze, M., Münzel, T., Förstermann, U. J. Am. Coll. Cardiol. (2006) [Pubmed]
  11. NADPH oxidase activity and function are profoundly greater in cerebral versus systemic arteries. Miller, A.A., Drummond, G.R., Schmidt, H.H., Sobey, C.G. Circ. Res. (2005) [Pubmed]
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