Source:http://linkedlifedata.com/resource/pubmed/id/20416349
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2010-5-31
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pubmed:abstractText |
Urotensin II (UII) a potent vasoactive peptide is upregulated in the failing heart and promotes cardiomyocytes hypertrophy, in particular through mitogen-activated protein kinases. However, the regulation by UII of GSK-3beta, a recognized pivotal signaling element of cardiac hypertrophy has not yet been documented. We therefore investigated in adult cardiomyocytes, if UII phosphorylates GSK-3beta and Akt, one of its upstream regulators and stabilizes beta-catenin, a GSK-3beta dependent nuclear transcriptional co-activator. Primary cultures of adult rat cardiomyocytes were stimulated for 48h with UII. Cell size and protein/DNA contents were determined. Phosphorylated and total forms of Akt, GSK-3beta and the total amount of beta-catenin were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the chemical phosphatidyl-inositol-3-kinase inhibitor, LY294002, and urantide, a competitive UII receptor antagonist. UII increased cell size and the protein/DNA ratio, consistent with a hypertrophic response. UII also increased phosphorylation of Akt and its downstream target GSK-3beta. beta-Catenin protein levels were increased. All of these effects of UII were prevented by LY294002, and urantide. The UII-induced adult cardiomyocytes hypertrophy involves the Akt/GSK-3beta signaling pathways and is accompanied by the stabilization of the beta-catenin. All these effects are abolished by competitive inhibition of the UII receptor, consistent with new therapeutic perspectives for heart failure treatment.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Urotensins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/urotensin II
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1873-5169
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1326-33
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:20416349-Animals,
pubmed-meshheading:20416349-Cell Size,
pubmed-meshheading:20416349-Glycogen Synthase Kinase 3,
pubmed-meshheading:20416349-Male,
pubmed-meshheading:20416349-Myocytes, Cardiac,
pubmed-meshheading:20416349-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20416349-Rats,
pubmed-meshheading:20416349-Signal Transduction,
pubmed-meshheading:20416349-Urotensins,
pubmed-meshheading:20416349-beta Catenin
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pubmed:year |
2010
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pubmed:articleTitle |
Urotensin II induction of adult cardiomyocytes hypertrophy involves the Akt/GSK-3beta signaling pathway.
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pubmed:affiliation |
Université catholique de Louvain, Unit of Diabetes and Nutrition, B-1200 Brussels, Belgium. damien.gruson@uclouvain.be
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pubmed:publicationType |
Journal Article
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