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Urocortin-induced cardiomyocytes hypertrophy is associated with regulation of the GSK-3β pathway

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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.

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Authors and Affiliations

  1. 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, Noémie Decroly, Pascale Lause, Jean-Marie Ketelslegers & Jean-Paul Thissen

  2. Pôle de recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires St-Luc and Université Catholique de Louvain, Brussels, Belgium

    Audrey Ginion, Jean-Louis Vanoverschelde & Luc Bertrand

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  1. Damien Gruson
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  2. Audrey Ginion
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  3. Noémie Decroly
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  4. Pascale Lause
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  5. Jean-Louis Vanoverschelde
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  6. Jean-Marie Ketelslegers
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  7. Luc Bertrand
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  8. Jean-Paul Thissen
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Correspondence to Damien Gruson.

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Gruson, D., Ginion, A., Decroly, N. et al. Urocortin-induced cardiomyocytes hypertrophy is associated with regulation of the GSK-3β pathway. Heart Vessels 27, 202–207 (2012). https://doi.org/10.1007/s00380-011-0141-5

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  • DOI: https://doi.org/10.1007/s00380-011-0141-5

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