Identification of Renox, an NAD(P)H oxidase in kidney

Oxygen sensing is essential for homeostasis in all aerobic organisms, but i ts mechanism is poorly understood. Data suggest that a phagocytic-like NAD( P)H oxidase producing reactive oxygen species serves as a primary sensor fo r oxygen. We have characterized a source of superoxide anions in the kidney that we refer to as a renal NAD(P)H oxidase or Renox. Renox is homologous to gp91(phox) (91-kDa subunit of the phagocyte oxidase), the electron-trans porting subunit of phagocytic NADPH oxidase. and contains all of the struct ural motifs considered essential for binding of heme, flavin, and nucleotid e, In situ RNA hybridization revealed that renox is highly expressed at the site of erythropoietin production in the renal cortex, showing the greates t accumulation of renox mRNA in proximal convoluted tubule epithelial cells . NIH 3T3 fibroblasts overexpressing transfected Renox show increased produ ction of superoxide and develop signs of cellular senescence. Our data sugg est that Renox, as a renal source of reactive oxygen species, is a likely c andidate for the oxygen sensor function regulating oxygen-dependent gene ex pression and may also have a role in the development of inflammatory proces ses in the kidney.