The nox family of NADPH oxidases that deliberately produce reactive oxygen species

Hideki Sumimoto, Reiko Minakami, Kei Miyano

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Reactive oxygen species (ROS) are classically considered as harmful by- products in aerobic metabolism; on the other hand, they are also deliberately produced by the Nox family NADPH oxidases on the membrane of a variety of cells. The human genome encodes seven members of the family: five Nox proteins (Nox1-Nox5) and the two dual oxidases Duox1 and Duox2 that produce superoxide or hydrogen peroxide as the 'true' primary product. Nox/Duox oxidases, except the constitutively active enzyme Nox4, are regulated via intracellular signal transduction. Activation of Nox1-3 requires binding of their stable membrane partner p22phox to the soluble protein p47phox (or its homologue Noxo1) complexed with the oxidase activator p67phox (or its related protein Noxa1), an event that is triggered by stimulus- induced phosphorylation of p47phox; the small GTPase Rac is upon cell stimulation converted to the GTP- bound form and subsequently interacts with p67phox or Noxa1, leading to oxidase activation. Nox5 as well as Duox1/2 harbors an N- terminal cytoplasmic extension with Ca2+- binding EF- hand motifs and is thus effectively activated by elevation in the intracellular concentration of Ca2+. The phagocyte oxidase Nox2 plays a crucial role in host defense by producing microbicidal ROS during phagocytosis. This oxidase also appears to function in immunoregulation, since genetic ablation of the Nox2 system causes not only severe pyrogenic infections but also non- infectious granulomatous inflammation similar to inflammatory bowel diseases. Both Nox1 and Duox2 are highly expressed in epithelial cells of the gastrointestinal tract, and could be involved in digestive diseases.

Original languageEnglish
Title of host publicationFree Radical Biology in Digestive Diseases
PublisherS. Karger AG
Pages23-34
Number of pages12
Volume29
ISBN (Electronic)9783805596107
ISBN (Print)9783805596091
DOIs
Publication statusPublished - Dec 21 2010

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All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Sumimoto, H., Minakami, R., & Miyano, K. (2010). The nox family of NADPH oxidases that deliberately produce reactive oxygen species. In Free Radical Biology in Digestive Diseases (Vol. 29, pp. 23-34). S. Karger AG. https://doi.org/10.1159/000319935