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.
MeSH terms
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Animals
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Blotting, Western
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Cardiomegaly / enzymology*
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Cardiomegaly / pathology
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Cardiomegaly / prevention & control
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Cell Size* / drug effects
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Cells, Cultured
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Chromones / pharmacology
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Corticotropin-Releasing Hormone / pharmacology
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Glycogen Synthase Kinase 3 / metabolism*
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Glycogen Synthase Kinase 3 beta
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Male
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Morpholines / pharmacology
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / enzymology*
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Myocytes, Cardiac / pathology
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Peptide Fragments / pharmacology
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Phosphatidylinositol 3-Kinase / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Protein Stability
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Rats, Wistar
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Receptors, Neuropeptide / antagonists & inhibitors
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Receptors, Neuropeptide / metabolism
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Signal Transduction* / drug effects
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Urocortins / metabolism*
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beta Catenin / metabolism
Substances
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Chromones
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Ctnnb1 protein, rat
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Morpholines
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Peptide Fragments
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Receptors, Neuropeptide
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Urocortins
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beta Catenin
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astressin
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Corticotropin-Releasing Hormone
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Phosphatidylinositol 3-Kinase
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, rat
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Proto-Oncogene Proteins c-akt
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Glycogen Synthase Kinase 3