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. 2003 Aug 15;374(Pt 1):63–69. doi: 10.1042/BJ20030326

Hepatocyte growth factor activates endothelial nitric oxide synthase by Ca(2+)- and phosphoinositide 3-kinase/Akt-dependent phosphorylation in aortic endothelial cells.

Kennedy Makondo 1, Kazuhiro Kimura 1, Naoki Kitamura 1, Takanori Kitamura 1, Daisuke Yamaji 1, Bae Dong Jung 1, Masayuki Saito 1
PMCID: PMC1223578  PMID: 12757411

Abstract

Hepatocyte growth factor (HGF) causes endothelium-dependent vasodilation, but its relation to endothelial nitric oxide synthase (eNOS) activity remains to be elucidated. Treatment of bovine aortic endothelial cells with HGF increased eNOS activity within minutes, accompanied by an increase of activity-related site-specific phosphorylation of eNOS. The phosphorylation was completely abolished by pretreatment of the cells with a phosphoinositide 3-kinase (PI3K) inhibitor (wortmannin) and by transfection of dominant-negative Akt, and the enzyme activity was inhibited by wortmannin. In addition, eNOS activity and phosphorylation were abolished by pretreatment of the cells with an intracellular Ca(2+)-chelator, bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM), with a suppression of Akt phosphorylation. These results suggest that HGF stimulates eNOS activity by a PI3K/Akt-dependent phosphorylation in a Ca(2+)-sensitive manner in vascular endothelial cells.

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Selected References

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