title: Urocortin-induced cardiomyocytes hypertrophy is associated with regulation of the GSK-3β pathway.
abstract: Urocortin-1 (UCN), a member of the corticotropin-releasing factor, is a cardioprotective peptide, and is also involved in cardiac hypertrophy. The involvement of GSK-3β, a pivotal kinase in cardiac hypertrophy, in response to UCN is not yet documented. Cardiomyocytes from adult rats were stimulated for 48 h with UCN. Cell size, protein, and DNA contents were determined. Phosphorylated and total forms GSK-3β and the total amount of β-catenin were quantified by Western immunoblots. The effects of astressin, a UCN competitive receptor antagonist, were also evaluated. UCN increased cell size and the protein-to-DNA ratio, in accordance with a hypertrophic response. This effect was associated with increased phosphorylation of GSK-3β and marked accumulation of β-catenin, a downstream element to GSK-3β. All these effects were prevented by astressin and LY294002, an inhibitor of the phosphatidyl-inositol-3-kinase. UCN-induced cardiomyocytes hypertrophy is associated with regulation of GSK-3β, a pivotal kinase involved in cardiac hypertrophy, in a PI3K-dependent manner. Furthermore, the pharmacological blockade of UCN receptors was able to prevent UCN-induced hypertrophy, which leads to inhibition of the Akt/GSK-3β pathway.
authors.affiliation: Pôle de Recherche en Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires St-Luc and Université Catholique de Louvain, Tour Claude Bernard, 54 Avenue Hippocrate, 1200 Brussels, Belgium. damien.gruson@uclouvain.be
authors.forename: Damien
authors.initials: D
authors.lastname: Gruson
authors.forename: Audrey
authors.initials: A
authors.lastname: Ginion
authors.forename: Noémie
authors.initials: N
authors.lastname: Decroly
authors.forename: Pascale
authors.initials: P
authors.lastname: Lause
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vanoverschelde
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ketelslegers
authors.forename: Luc
authors.initials: L
authors.lastname: Bertrand
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thissen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054832:Urocortins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002867:Chromones; C495268:Ctnnb1 protein, rat; D009025:Morpholines; D010446:Peptide Fragments; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D018013:Receptors, Neuropeptide; D054832:Urocortins; D051176:beta Catenin; C104416:astressin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003346:Corticotropin-Releasing Hormone; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3