title: A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes.
abstract: Superoxide and its derivatives are increasingly implicated in the regulation of physiological functions from oxygen sensing and blood pressure regulation to lymphocyte activation and sperm-oocyte fusion. Here we describe a novel superoxide-generating NADPH oxidase referred to as NADPH oxidase 5 (NOX5). NOX5 is distantly related to the gp91(phox) subunit of the phagocyte NADPH oxidase with conserved regions crucial for the electron transport (NADPH, FAD and heme binding sites). However, NOX5 has a unique N-terminal extension that contains three EF hand motifs. The mRNA of NOX5 is expressed in pachytene spermatocytes of testis and in B- and T-lymphocyte-rich areas of spleen and lymph nodes. When heterologously expressed, NOX5 was quiescent in unstimulated cells. However, in response to elevations of the cytosolic Ca(2+) concentration it generated large amounts of superoxide. Upon Ca(2+) activation, NOX5 also displayed a second function: it became a proton channel, presumably to compensate charge and pH alterations due to electron export. In summary, we have identified a novel NADPH oxidase that generates superoxide and functions as a H(+) channel in a Ca(2+)-dependent manner. NOX5 is likely to be involved in Ca(2+)-activated, redox-dependent processes of spermatozoa and lymphocytes such as sperm-oocyte fusion, cell proliferation, and cytokine secretion.
authors.affiliation: Biology of Aging Laboratory, Department of Geriatrics, Geneva University Hospitals, Ch. du Petit-Bel-Air 2, CH-1225 Geneva, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Bánfi
authors.forename: G
authors.initials: G
authors.lastname: Molnár
authors.forename: A
authors.initials: A
authors.lastname: Maturana
authors.forename: K
authors.initials: K
authors.lastname: Steger
authors.forename: B
authors.initials: B
authors.lastname: Hegedûs
authors.forename: N
authors.initials: N
authors.lastname: Demaurex
authors.forename: K H
authors.initials: KH
authors.lastname: Krause
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D017136:Ion Transport; D008198:Lymph Nodes / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011522:Protons; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism; D013737:Testis / Q000201:enzymology*
chemical_list: D008565:Membrane Proteins; D011522:Protons; D013481:Superoxides; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; C431571:NOX5 protein, human; D002118:Calcium