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Modulation of cardiac cAMP signaling by AMPK and its adjustments in pressure overload-induced myocardial dysfunction in rat and mouse.
Garnier, Anne; Leroy, Jérôme; Deloménie, Claudine; Mateo, Philippe; Viollet, Benoit; Veksler, Vladimir; Mericskay, Mathias; Ventura-Clapier, Renée; Piquereau, Jérôme.
Afiliación
  • Garnier A; UMR-S 1180, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Orsay, France.
  • Leroy J; UMR-S 1180, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Orsay, France.
  • Deloménie C; ACTAGen, UMS IPSIT, Univ. Paris-Sud, Université Paris Saclay, Orsay, France.
  • Mateo P; Physics for Medecine, Ecole Supérieure de Physique Chimie Industrielles de Paris, INSERM U1273, CNRS UMR8063, PSL University, Paris, France.
  • Viollet B; Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
  • Veksler V; UMR-S 1180, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Orsay, France.
  • Mericskay M; UMR-S 1180, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Orsay, France.
  • Ventura-Clapier R; UMR-S 1180, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Orsay, France.
  • Piquereau J; UMR-S 1180, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Orsay, France.
PLoS One ; 18(9): e0292015, 2023.
Article en En | MEDLINE | ID: mdl-37733758
The beta-adrenergic system is a potent stimulus for enhancing cardiac output that may become deleterious when energy metabolism is compromised as in heart failure. We thus examined whether the AMP-activated protein kinase (AMPK) that is activated in response to energy depletion may control the beta-adrenergic pathway. We studied the cardiac response to beta-adrenergic stimulation of AMPKα2-/- mice or to pharmacological AMPK activation on contractile function, calcium current, cAMP content and expression of adenylyl cyclase 5 (AC5), a rate limiting step of the beta-adrenergic pathway. In AMPKα2-/- mice the expression of AC5 (+50%), the dose response curve of left ventricular developed pressure to isoprenaline (p<0.001) or the response to forskolin, an activator of AC (+25%), were significantly increased compared to WT heart. Similarly, the response of L-type calcium current to 3-isobutyl-l-methylxanthine (IBMX), a phosphodiesterase inhibitor was significantly higher in KO (+98%, p<0.01) than WT (+57%) isolated cardiomyocytes. Conversely, pharmacological activation of AMPK by 5-aminoimidazole-4-carboxamide riboside (AICAR) induced a 45% decrease in AC5 expression (p<0.001) and a 40% decrease of cAMP content (P<0.001) as measured by fluorescence resonance energy transfer (FRET) compared to unstimulated rat cardiomyocytes. Finally, in experimental pressure overload-induced cardiac dysfunction, AMPK activation was associated with a decreased expression of AC5 that was blunted in AMPKα2-/- mice. The results show that AMPK activation down-regulates AC5 expression and blunts the beta-adrenergic cascade. This crosstalk between AMPK and beta-adrenergic pathways may participate in a compensatory energy sparing mechanism in dysfunctional myocardium.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas Activadas por AMP / Insuficiencia Cardíaca Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas Activadas por AMP / Insuficiencia Cardíaca Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos