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

James Reihill, Marie-Ann Ewart, Grahame Hardie, Ian Salt

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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 Ca2+/calmodulin-dependent protein kinase kinase inhibitor, STO-609. Stimulation of AMPK via Ca2+/calmodulin-dependent protein kinase kinase represents a novel signalling mechanism utilised by VEGF in endothelial cells that contributes to eNOS phosphorylation and NO production.
Original languageEnglish
Pages (from-to)1084
Number of pages4
JournalBiochemical and Biophysical Research Communications
Publication statusPublished - 23 Mar 2007

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