Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR

Briones, A.M., Tabet, F., Callera, G.E., Montezano, A.C., Yogi, A., He, Y., Quinn, M.T., Salaices, M. and Touyz, R.M. (2011) Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR. Journal of the American Society of Hypertension, 5(3), pp. 137-153. (doi:10.1016/j.jash.2011.02.001)

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Publisher's URL: http://dx.doi.org/10.1016/j.jash.2011.02.001

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 •O2− production. Nox1 regulation by Ang II, but not by ET-1, may be important in •O2− formation in VSMCs from SHR.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montezano, Dr Augusto and Touyz, Professor Rhian
Authors: Briones, A.M., Tabet, F., Callera, G.E., Montezano, A.C., Yogi, A., He, Y., Quinn, M.T., Salaices, M., and Touyz, R.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of the American Society of Hypertension
ISSN:1933-1711
ISSN (Online):1878-7436
Published Online:17 March 2011

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