Nox4 as the Major Catalytic Component of an Endothelial NAD(P)H Oxidase

Abstract

Background-Recent evidence has suggested that reactive oxygen species are important signaling molecules in vascular cells and play a pivotal role in the development of vascular diseases. The activity of NAD(P)H oxidase has been identified as the major source of reactive oxygen species in vascular endothelial cells. However, the precise molecular structure and the mechanism of activation of the oxidase have remained poorly understood. Methods and Results-Here, we investigated the molecular identities and the superoxide-producing activity of endothelial NAD(P)H oxidase. We found that Nox4, a homologue of gp91phox/Nox2, was abundantly expressed in endothelial cells. The expression of Nox4 in endothelial cells markedly exceeded that of other Nox proteins, including gp91phox/Nox2, and was affected by cell growth. Using electron spin resonance and chemiluminescence, we measured the superoxide production and found that the endothelial membranes had an NAD(P)H-dependent superoxide-producing activity comparable to that of the neutrophil membranes, whereas the activity was not enhanced by the 2 recombinant proteins p47phox and p67phox, in contrast to that of the neutrophil membranes. Downregulation of Nox4 by an antisense oligonucleotide reduced superoxide production in endothelial cells in vivo and in vitro. Conclusions-These

Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

“…There have been a few studies on the expression of Nox family mRNAs and proteins in different kinds of human cells [15][16][17][18][19][20][21], but very few studies on the expression of Nox1 to Nox5 in the salivary glands even though it has been reported that salivary gland ducts express Duox1 [27]. platelet-derived growth factor induce the expression of Nox1 in vascular smooth muscle cells [28][29][30][31][32][33].…”

“…Nox2 (gp91 phox ) is predominantly expressed in phagocytes [15] and Nox3 exists in the inner ear of rodents, and is essential for the otoconium formation [18]. Nox4 is highly expressed in epithelial cells of renal tubules [19] and also in vascular endothelial cells [20]. Nox5 is predominantly expressed in the testis and spleen but its biological role is unknown [21].…”

Direct Interaction of the Novel Nox Proteins with p22phox Is Required for the Formation of a Functionally Active NADPH Oxidase

“…The homologue Nox1 has been suggested to have a role in the host defense of epithelial cells (11) and to contribute to signaling leading to hypertrophy and angiogenesis and even tumor formation (7,12). Little is known about the functions of Nox4, but high expression of Nox4 has been suggested to induce senescence (8), and evidence indicates that Nox4 may also be involved in redox-mediated signal transduction in mesangial cells (13), adipocytes (14), and endothelial cells (15).…”

Effects of red grape juice polyphenols in NADPH oxidase subunit expression in human neutrophils and mononuclear blood cells

“…NOX2 (previously named gp91phox) homologues (NOX1, 3, 4, 5, dual oxidase (DUOX)1 and DUOX2) have been characterised in different cell types, including vascular cells (4) . NOX1 and NOX4 are abundantly expressed in vascular smooth muscle cells and endothelial cells, respectively (6,7) . In contrast to phagocytic cells, vascular cells produce superoxide under basal, non-stimulated conditions but to a significantly lesser extent than phagocytes (8) .…”