title: Nox family NADPH oxidases: Molecular mechanisms of activation.
abstract: NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS). Numerous homologue-specific mechanisms control the activity of this enzyme family involving calcium, free fatty acids, protein-protein interactions, intracellular trafficking, and posttranslational modifications such as phosphorylation, acetylation, or sumoylation. After a brief review on the classic pathways of Nox activation, this article will focus on novel mechanisms of homologue-specific activity control and on cell-specific aspects which govern Nox activity. From these findings of the recent years it must be concluded that the activity control of Nox enzymes is much more complex than anticipated. Moreover, depending on the cellular activity state, Nox enzymes are selectively activated or inactivated. The complex upstream signaling aspects of these events make the development of "intelligent" Nox inhibitors plausible, which selectively attenuate disease-related Nox-mediated ROS formation without altering physiological signaling ROS. This approach might be of relevance for Nox-mediated tissue injury in ischemia-reperfusion and inflammation and also for chronic Nox overactivation as present in cancer initiation and cardiovascular disease.
authors.affiliation: Institut für Kardiovaskuläre Physiologie, Goethe-Universität Frankfurt, Frankfurt, Germany. Electronic address: r.brandes@em.uni-frankfurt.de.
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Brandes
authors.affiliation: ECCPS, Justus-Liebig-Universität, Member of the DZL, Giessen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.affiliation: Institut für Kardiovaskuläre Physiologie, Goethe-Universität Frankfurt, Frankfurt, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schröder
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: Activity control; NADPH oxidase; Nox; Oxygen-derived free radicals; Phosphorylation; p22phox