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

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 geneticablation 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
Pages23-34
Number of pages12
Volume29
DOIs
Publication statusPublished - Dec 2010

Publication series

NameFrontiers of Gastrointestinal Research
Volume29
ISSN (Print)03020665

Fingerprint

NADPH Oxidase
Reactive Oxygen Species
Oxidoreductases
EF Hand Motifs
Proteins
Membranes
Monomeric GTP-Binding Proteins
Human Genome
Phagocytes
Guanosine Triphosphate
Inflammatory Bowel Diseases
Phagocytosis
Superoxides
Hydrogen Peroxide
Gastrointestinal Tract
Signal Transduction
Epithelial Cells
Phosphorylation
Inflammation
Enzymes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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). (Frontiers of Gastrointestinal Research; Vol. 29). https://doi.org/10.1159/00031993512

The Nox family of NADPH oxidases that deliberately produce reactive oxygen species. / Sumimoto, Hideki; Minakami, Reiko; Miyano, Kei.

Free Radical Biology in Digestive Diseases. Vol. 29 2010. p. 23-34 (Frontiers of Gastrointestinal Research; Vol. 29).

Research output: Chapter in Book/Report/Conference proceedingChapter

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, Frontiers of Gastrointestinal Research, vol. 29, pp. 23-34. https://doi.org/10.1159/00031993512
Sumimoto H, Minakami R, Miyano K. The Nox family of NADPH oxidases that deliberately produce reactive oxygen species. In Free Radical Biology in Digestive Diseases. Vol. 29. 2010. p. 23-34. (Frontiers of Gastrointestinal Research). https://doi.org/10.1159/00031993512
Sumimoto, Hideki ; Minakami, Reiko ; Miyano, Kei. / The Nox family of NADPH oxidases that deliberately produce reactive oxygen species. Free Radical Biology in Digestive Diseases. Vol. 29 2010. pp. 23-34 (Frontiers of Gastrointestinal Research).
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