http://www.cnr.it/ontology/cnr/individuo/prodotto/ID4889

cAMP-mediated beta-adrenergic signaling negatively regulates Gq-coupled receptor-mediated fetal gene response in cardiomyocytes (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

cAMP-mediated beta-adrenergic signaling negatively regulates Gq-coupled receptor-mediated fetal gene response in cardiomyocytes (Articolo in rivista) (literal)

Anno

2008-01-01T00:00:00+01:00 (literal)

Alternative label

Patrizio M.; Vago V.; Musumeci M.; Fecchi K.; Sposi N.M.; Mattei E.; Catalano L.; Stati T.; Marano G. (2008)
cAMP-mediated beta-adrenergic signaling negatively regulates Gq-coupled receptor-mediated fetal gene response in cardiomyocytes
in Journal of Molecular and Cellular Cardiology; Elsevier, Amsterdam (Paesi Bassi)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Patrizio M.; Vago V.; Musumeci M.; Fecchi K.; Sposi N.M.; Mattei E.; Catalano L.; Stati T.; Marano G. (literal)

Pagina inizio

761 (literal)

Pagina fine

769 (literal)

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Epub 2008 Sep 25 Impact Factor 5,499 (literal)

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45(6) (literal)

Rivista

Journal of Molecular and Cellular Cardiology (Rivista)

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9 (literal)

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Cardiomyocytes (literal)

Note

ISI Web of Science (WOS) (literal)

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a) Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; b) Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy; c) Department of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, Rome, Italy; d) Italian National Blood Center, Rome, Italy (literal)

Titolo

cAMP-mediated beta-adrenergic signaling negatively regulates Gq-coupled receptor-mediated fetal gene response in cardiomyocytes (literal)

Abstract

The treatment with beta-blockers causes an enhancement of the norepinephrine-induced fetal gene response in cultured cardiomyocytes. Here, we tested whether the activation of cAMP-mediated beta-adrenergic signaling antagonizes alpha(1)-adrenergic receptor (AR)-mediated fetal gene response. To address this question, the fetal gene program, of which atrial natriuretic peptide (ANP) and the beta-isoform of myosin heavy chain are classical members, was induced by phenylephrine (PE), an alpha(1)-AR agonist. In cultured neonatal rat cardiomyocytes, we found that stimulation of beta-ARs with isoproterenol, a beta-AR agonist, inhibited the fetal gene expression induced by PE. Similar results were also observed when cardiomyocytes were treated with forskolin (FSK), a direct activator of adenylyl cyclase, or 8-CPT-6-Phe-cAMP, a selective activator of protein kinase A (PKA). Conversely, the PE-induced fetal gene expression was further upregulated by H89, a selective PKA inhibitor. To evaluate whether these results could be generalized to Gq-mediated signaling and not specifically to alpha(1)-ARs, cardiomyocytes were treated with prostaglandin F(2)alpha, another Gq-coupled receptor agonist, which is able to promote fetal gene expression. This treatment caused an increase of both ANP mRNA and protein levels, which was almost completely abolished by FSK treatment. The capability of beta-adrenergic signaling to regulate the fetal gene expression was also evaluated in vivo conditions by using beta1- and beta2-AR double knockout mice, in which the predominant cardiac beta-AR subtypes are lacking, or by administering isoproterenol (ISO), a beta-AR agonist, at a subpressor dose. A significant increase of the fetal gene expression was found in beta(1)- and beta(2)-AR gene deficient mice. Conversely, we found that ANP, beta-MHC and skACT mRNA levels were significantly decreased in ISO-treated hearts. Collectively, these data indicate that cAMP-mediated beta-adrenergic signaling negatively regulates Gq cascade activation-induced fetal gene expression in cultured cardiomyocytes and that this inhibitory regulation is already operative in the mouse heart under physiological conditions. (literal)

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