Linked Life Data

20213742

Source:http://linkedlifedata.com/resource/pubmed/id/20213742

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-4-22
pubmed:abstractText
Accumulating evidences point to a significant role for the chromogranin A (CgA)-derived peptide vasostatin 1 (VS-1) in the protective modulation of the cardiovascular activity, because of its ability to counteract the adrenergic signal. We have recently shown that VS-1 induces a PI3K-dependent-nitric oxide (NO) release by endothelial cells, contributing to explain the mechanism of its cardio-suppressive and vasodilator properties. However, the cellular processes upstream the eNOS activation exerted by this peptide are still unknown, as typical high-affinity receptors have not been identified. Here we hypothesize that in endothelial cells VS-1 acts, on the basis of its cationic and amphipathic properties, as a cell penetrating peptide, binding to heparan sulfate proteoglycans (HSPGs) and activating eNOS phosphorylation (Ser1179) through a PI3K-dependent, endocytosis-coupled mechanism. In bovine aortic endothelial cells (BAE-1 cells) endocytotic vesicles trafficking was quantified by confocal microscopy with a water-soluble membrane dye; caveolin 1 (Cav1) shift from plasma membrane was studied by immunofluorescence staining; VS-1-dependent eNOS phosphorylation was assessed by immunofluorescence and immunoblot analysis. Our experiments demonstrate that VS-1 induces a marked increase in the caveolae-dependent endocytosis, (115 +/- 23% endocytotic spots/cell/field in VS-1-treated cells with respect to control cells), that is significantly reduced by both heparinase III (HEP, 17 +/- 15% above control) and Wortmannin (Wm, 7 +/- 22% above control). Heparinase, Wortmannin, and methyl-beta-cyclodextrin (MbetaCD) abolish the VS-1-dependent eNOS phosphorylation (P(Ser1179)eNOS). These results suggest a novel signal transduction pathway for endogenous cationic and amphipathic peptides in endothelial cells: HSPGs interaction and caveolae endocytosis, coupled with a PI3K-dependent eNOS phosphorylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
70-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Vasostatin 1 activates eNOS in endothelial cells through a proteoglycan-dependent mechanism.
pubmed:affiliation
Dipartimento di Biologia Animale e dell'Uomo, Università di Torino, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't