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A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes

Steger, Klaus
Hegedus, B.
Published in Journal of Biological Chemistry. 2001, vol. 276, no. 40, p. 37594-37601
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.
Keywords Amino Acid SequenceAnimalsCOS CellsCalcium/ metabolism/physiologyCytosol/metabolismElectrophysiologyGenomeHela CellsHumansIn Situ HybridizationIon TransportLymph Nodes/ enzymologyMaleMembrane Proteins/genetics/ metabolism/physiologyMolecular Sequence DataNADPH Oxidase/chemistry/genetics/ metabolism/physiologyPolymerase Chain ReactionProtonsSequence Homology, Amino AcidSpleen/ enzymologySuperoxides/metabolismTestis/ enzymology
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Other version: http://www.jbc.org/content/276/40/37594.full.pdf
PMID: 11483596
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