Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway

Carmine Vecchione, Angelo Maffei, Salvatore Colella, Alessandra Aretini, Roberta Poulet, Giacomo Frati, Maria Teresa Gentile, Luigi Fratta, Valentina Trimarco, Bruno Trimarco, Giuseppe Lembo

Research output: Contribution to journalArticlepeer-review

Abstract

Recent evidence suggests that besides its action on the central nervous system, leptin can modulate vascular tone through local mechanisms involving nitric oxide (NO) release. In this study, using a fluorescent probe for direct determination of NO, we demonstrated both in endothelial cells and in vessels that leptin is able to stimulate NO release. The effect of leptin on NO is abolished by erbstatin A, a Ca2+-independent tyrosine kinase inhibitor, whereas it is not influenced by calcium removal or by other protein phosphorylation inhibitors, such as genistein (an ATP-dependent tyrosine-kinase inhibitor) or wortmannin and LY294002 (two different phosphatidylinositol [PI] 3-kinase inhibitors). Accordingly, leptin-induced vasorelaxation in aortic rings was abolished only by erbstatin A. Furthermore, immunoblotting studies revealed that leptin evokes Akt phosphorylation, with a comparable time course in both endothelial cells and vessels. Also in this experimental system, the effect of leptin was abolished by erbstatin A and not by other inhibitors. Finally, a considerable increase in endothelial NO synthase (eNOS) phosphorylation in Ser1177 was found when vessels were treated with leptin. In conclusion, leptin induces NO production by activating a PI 3-kinase-independent Akt-eNOS phosphorylation pathway.

Original languageEnglish
Pages (from-to)168-173
Number of pages6
JournalDiabetes
Volume51
Issue number1
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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