A Ca2+-activated NADPH Oxidase in Testis, Spleen, and Lymph Nodes

Botond Bánfi, Gergely Molnár, Andres Maturana, Klaus Steger, Balázs Hegedûs, Nicolas Demaurex, Karl Heinz Krause

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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 gp91phox 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 Ca2+ concentration it generated large amounts of superoxide. Upon Ca2+ 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 Ca2+-dependent manner. NOX5 is likely to be involved in Ca2+-activated, redox-dependent processes of spermatozoa and lymphocytes such as sperm-oocyte fusion, cell proliferation, and cytokine secretion.

Original languageEnglish
Pages (from-to)37594-37601
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number40
DOIs
Publication statusPublished - Oct 5 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Bánfi, B., Molnár, G., Maturana, A., Steger, K., Hegedûs, B., Demaurex, N., & Krause, K. H. (2001). A Ca2+-activated NADPH Oxidase in Testis, Spleen, and Lymph Nodes. Journal of Biological Chemistry, 276(40), 37594-37601. https://doi.org/10.1074/jbc.M103034200