AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production

Reihill, J.A., Ewart, M.-A., Hardie, D.G. and Salt, I. (2007) AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production. Biochemical and Biophysical Research Communications, 354(4), pp. 1084-1088. (doi: 10.1016/j.bbrc.2007.01.110)

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Vascular endothelial growth factor (VEGF) is an important regulator of endothelial cell function. VEGF stimulates NO production, proposed to be a result of phosphorylation and activation of endothelial NO synthase (eNOS) at Ser1177. Phosphorylation of eNOS at this site also occurs after activation of AMP-activated protein kinase (AMPK) in cultured endothelial cells. We therefore determined whether AMPK mediates VEGF-stimulated NO synthesis in endothelial cells. VEGF caused a rapid, dose-dependent stimulation of AMPK activity, with a concomitant increase in phosphorylation of eNOS at Ser1177. Infection of endothelial cells with an adenovirus expressing a dominant negative mutant AMPK partially inhibited both VEGF-stimulated eNOS Ser1177 phosphorylation and NO production. VEGF-stimulated AMPK activity was completely inhibited by the Ca(2<sup>+</sup>)/calmodulin-dependent protein kinase kinase inhibitor, STO-609. Stimulation of AMPK via Ca(2<sup>+</sup>)/calmodulin-dependent protein kinase kinase represents a novel signalling mechanism utilised by VEGF in endothelial cells that contributes to eNOS phosphorylation and NO production.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Reihill, Mr James and Ewart, Dr Marie-Ann and Salt, Dr Ian
Authors: Reihill, J.A., Ewart, M.-A., Hardie, D.G., and Salt, I.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Biochemical and Biophysical Research Communications
Journal Abbr.:BBRC
ISSN (Online):1090-2104
Published Online:29 January 2007

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