Introduction: The Chromogranin A (CgA)-derived peptide Catestatin (CST) is a novel regulator of cardiac function and blood pressure, being able to induce anti-adrenergic, vasodilatory and cardioprotective effects, which are mainly due to nitric oxide (NO) release from endothelial cells. The cellular processes upstream eNOS activation exerted by CST are still unknown, mainly because typical high-affinity CST receptors have not been identified. We thus hypothesized that, on the basis of its cationic and amphipathic properties, CST acts as a cell penetrating peptide, binding to heparan sulfate proteoglycans (HSPGs) and activating eNOS phosphorylation through a PI3K-dependent, endocytosis-coupled mechanism. Methods: In bovine aortic endothelial cells (BAE-1 cells), endocytotic vesicles trafficking was quantified by confocal microscopy with the membrane dye FM1-43; Caveolin (Cav)-1 shift from plasma membrane was studied by immunofluorescence staining and transfection with GFP-Cav; eNOS phosphorylation was assessed by immunofluorescence and immunoblot analysis. Results and Conclusions: CST markedly increased both caveolae-dependent endocytosis and eNOS phosphorylation in BAE-1 cell. These effects were reduced by both heparinase III and Wortmannin. Our results suggest a novel signal transduction pathway involved in the action of CST on endothelial cells: HSPGs interaction and caveolae endocytosis, coupled with a PI3K-dependent eNOS phosphorylation.

Catestatin induces NO synthesis in endothelial cells by stimulating caveolae endocytosis and PI3K-dependent eNOS phosphorylation / FORNERO S; BASSINO E; GALLO MP; LEVI R; TOTA B; ALLOATTI G. - In: ACTA PHYSIOLOGICA. - ISSN 1748-1708. - STAMPA. - 206 (S 692)(2012), pp. 185-185. ((Intervento presentato al convegno LXIII Congresso nazionale SIF tenutosi a Verona nel 21-23/09/2012.

Catestatin induces NO synthesis in endothelial cells by stimulating caveolae endocytosis and PI3K-dependent eNOS phosphorylation

FORNERO, SARA;BASSINO, ELEONORA;GALLO, Maria Pia;LEVI, Renzo;ALLOATTI, Giuseppe
2012

Abstract

Introduction: The Chromogranin A (CgA)-derived peptide Catestatin (CST) is a novel regulator of cardiac function and blood pressure, being able to induce anti-adrenergic, vasodilatory and cardioprotective effects, which are mainly due to nitric oxide (NO) release from endothelial cells. The cellular processes upstream eNOS activation exerted by CST are still unknown, mainly because typical high-affinity CST receptors have not been identified. We thus hypothesized that, on the basis of its cationic and amphipathic properties, CST acts as a cell penetrating peptide, binding to heparan sulfate proteoglycans (HSPGs) and activating eNOS phosphorylation through a PI3K-dependent, endocytosis-coupled mechanism. Methods: In bovine aortic endothelial cells (BAE-1 cells), endocytotic vesicles trafficking was quantified by confocal microscopy with the membrane dye FM1-43; Caveolin (Cav)-1 shift from plasma membrane was studied by immunofluorescence staining and transfection with GFP-Cav; eNOS phosphorylation was assessed by immunofluorescence and immunoblot analysis. Results and Conclusions: CST markedly increased both caveolae-dependent endocytosis and eNOS phosphorylation in BAE-1 cell. These effects were reduced by both heparinase III and Wortmannin. Our results suggest a novel signal transduction pathway involved in the action of CST on endothelial cells: HSPGs interaction and caveolae endocytosis, coupled with a PI3K-dependent eNOS phosphorylation.
LXIII Congresso nazionale SIF
Verona
21-23/09/2012
206 (S 692)
185
185
FORNERO S; BASSINO E; GALLO MP; LEVI R; TOTA B; ALLOATTI G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/128715
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