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Gene Review

NOX3  -  NADPH oxidase 3

Homo sapiens

Synonyms: GP91-3, MOX-2, MOX2, Mitogenic oxidase 2, gp91phox homolog 3
 
 
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Disease relevance of NOX3

  • Microdissection and in situ hybridization studies demonstrated that NOX3 is localized to the vestibular and cochlear sensory epithelia and to the spiral ganglions [1].
  • Our data suggest that NOX3 is a relevant source of ROS generation in the cochlear and vestibular systems and that NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to ototoxic drugs [1].
 

High impact information on NOX3

  • We explored determinants of assembly of the multicomponent oxidases Nox1 and Nox3 and examined the involvement of Rac1 in their regulation [2].
  • As assessed by real-time PCR, NOX3 mRNA expression in the inner ear is at least 50-fold higher than in any other tissues where its expression has been observed (e.g. fetal kidney, brain, skull) [1].
  • Transfection of human embryonic kidney 293 cells with NOX3 revealed that it generates low levels of ROS on its own but produces high levels of ROS upon co-expression with cytoplasmic NOX subunits [1].
  • Unexpectedly, Nox3 was strongly activated by NOXO1 in the absence of NOXA1 or p67(phox) [3].
  • The unique regulation of Nox3 supports a model in which multiple interactions with regulatory subunits stabilize an active conformation of the catalytic subunit [3].
 

Biological context of NOX3

 

Anatomical context of NOX3

  • Cultured rat astrocytes express mRNAs encoding for the regulatory subunit p47(phox), NOX1, 2, and 4, and the dual oxidases (DUOX)1 and 2, but not NOX3 [5].
  • Cisplatin also increased the expression of cochlear NOX3 mRNA, a member of the superoxide generating NADPH oxidase family of proteins recently identified in the cochlea, inhibition of which decreased kidney injury molecule-1 expression [6].
  • Furthermore, only mAb 54.1 recognized full-length murine and human Nox3 expressed in HEK-293 cells, in immunoblots of alkali-stripped or detergent-solubilized membranes [7].
 

Other interactions of NOX3

  • Rac, albeit probably dispensable to the Nox3 activity, plays an essential role in activation of gp91phox [8].
  • We conclude that mAb 54.1 can serve as a probe of Nox3 and possibly other Nox proteins, if precautions are taken to remove GRP 58 and other crossreactive membrane-associated or detergent-insoluble proteins from the sample to be probed [7].

References

  1. NOX3, a superoxide-generating NADPH oxidase of the inner ear. Bánfi, B., Malgrange, B., Knisz, J., Steger, K., Dubois-Dauphin, M., Krause, K.H. J. Biol. Chem. (2004) [Pubmed]
  2. Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases. Ueyama, T., Geiszt, M., Leto, T.L. Mol. Cell. Biol. (2006) [Pubmed]
  3. Nox3 regulation by NOXO1, p47phox, and p67phox. Cheng, G., Ritsick, D., Lambeth, J.D. J. Biol. Chem. (2004) [Pubmed]
  4. Tissue distribution and putative physiological function of NOX family NADPH oxidases. Krause, K.H. Jpn. J. Infect. Dis. (2004) [Pubmed]
  5. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Reinehr, R., Görg, B., Becker, S., Qvartskhava, N., Bidmon, H.J., Selbach, O., Haas, H.L., Schliess, F., Häussinger, D. Glia (2007) [Pubmed]
  6. Expression of the kidney injury molecule 1 in the rat cochlea and induction by cisplatin. Mukherjea, D., Whitworth, C.A., Nandish, S., Dunaway, G.A., Rybak, L.P., Ramkumar, V. Neuroscience (2006) [Pubmed]
  7. Evaluation of two anti-gp91phox antibodies as immunoprobes for Nox family proteins: mAb 54.1 recognizes recombinant full-length Nox2, Nox3 and the C-terminal domains of Nox1-4 and cross-reacts with GRP 58. Baniulis, D., Nakano, Y., Nauseef, W.M., Banfi, B., Cheng, G., Lambeth, D.J., Burritt, J.B., Taylor, R.M., Jesaitis, A.J. Biochim. Biophys. Acta (2005) [Pubmed]
  8. Regulation of superoxide-producing NADPH oxidases in nonphagocytic cells. Takeya, R., Ueno, N., Sumimoto, H. Meth. Enzymol. (2006) [Pubmed]
 
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