title: Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR.
abstract: The functional significance and regulation of NAD(P)H oxidase (Nox) isoforms by angiotensin II (Ang II) and endothelin-1 (ET-1) in vascular smooth muscle cells (VSMCs) from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was studied. Expression of Nox1, Nox2, and Nox4 (gene and protein) and NAD(P)H oxidase activity were increased in SHR. Basal NAD(P)H oxidase activity was blocked by GKT136901 (Nox1/4 inhibitor) and by Nox1 siRNA in WKY cells and by siNOX1 and siNOX2 in SHR. Whereas Ang II increased expression of all Noxes in WKY, only Nox1 was influenced in SHR. Ang II-induced NAD(P)H activity was inhibited by siNOX1 in WKY and by siNOX1 and siNOX2 in SHR. ET-1 upregulated Nox expression only in WKY and increased NAD(P)H oxidase activity, an effect inhibited by siNOX1 and siNOX2. Nox1 co-localized with Nox2 but not with Nox4, implicating association between Nox1 and Nox2 but not between Nox1 and Nox4. These data highlight the complexity of Nox biology in VSMCs, emphasising that more than one Nox member, alone or in association, may be involved in NAD(P)H oxidase-mediated •O(2)(-) production. Nox1 regulation by Ang II, but not by ET-1, may be important in •O(2)(-) formation in VSMCs from SHR.
authors.affiliation: Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ontario, Canada.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Briones
authors.forename: Fatiha
authors.initials: F
authors.lastname: Tabet
authors.forename: Glaucia E
authors.initials: GE
authors.lastname: Callera
authors.forename: Augusto C
authors.initials: AC
authors.lastname: Montezano
authors.forename: Alvaro
authors.initials: A
authors.lastname: Yogi
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Mark T
authors.initials: MT
authors.lastname: Quinn
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D008562:Membrane Glycoproteins; D013481:Superoxides; D000804:Angiotensin II; D009247:NADH, NADPH Oxidoreductases; C500593:Cybb protein, rat; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C000614712:NOX1 protein, rat; C498911:Nox4 protein, rat