Dual cardiac contractile effects of the alpha2-AMPK deletion in low-flow ischemia and reperfusion
| Autor: | Carvajal, Karla, Zarrinpashneh, Elham, Szarszoi, Ondrej, Joubert, Frederic, Athea, Yoni, Mateo, Philippe, Gillet, Brigitte, Vaulont, Sophie, Viollet, Benoit, Bigard, Xavier, Bertrand, Luc, Ventura-Clapier, Renée, Hoerter, Jacqueline |
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| Přispěvatelé: | Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), Division de Cardiologie, Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, This work is supported by Institut National de la Santé et de la Recherche Médicale, France, by a grant of the Fondation de France, by a grant from the Fonds National de la Recherche Scientifique et Médicale, Belgium and by the European Commission (grant QLG1-CT-2001-01488), E. Z. by the Fonds Spéciaux de Recherche, UCL, Belgium. LB is Research Associate of the Fonds National de la Recherche Scientifique, Belgium., Ventura-Clapier, Renée |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
MESH: Enzyme Activation
MESH: Myocardium MESH: Myocardial Contraction MESH: Glycogen MESH: Phosphocreatine MESH: Multienzyme Complexes MESH: Mice Knockout MESH: Protein-Serine-Threonine Kinases [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system MESH: Adenosine Triphosphate MESH: Animals MESH: AMP-Activated Protein Kinases MESH: Oxygen Consumption MESH: Mice MESH: Pyruvic Acid energetics MESH: Kinetics MESH: Phosphorylation creatine kinase MESH: Energy Metabolism energetic cost of contractility MESH: Male MESH: Myocardial Reperfusion Injury glucose uptake rigor MESH: Fatty Acids [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system MESH: Glucose MESH: Creatine Kinase MM Form MESH: Myocardial Ischemia 31P NMR spectroscopy MESH: Cell Respiration MESH: Perfusion |
| Zdroj: | AJP-Heart and Circulatory Physiology AJP-Heart and Circulatory Physiology, 2007, 292 (6), pp.H3136-47. ⟨10.1152/ajpheart.00683.2006⟩ |
| ISSN: | 0363-6135 1522-1539 |
| DOI: | 10.1152/ajpheart.00683.2006⟩ |
| Popis: | International audience; Because the question "is AMP-activated protein kinase (AMPK) alpha(2)-isoform a friend or a foe in the protection of the myocardium against ischemia-reperfusion injury?" is still in debate, we studied the functional consequence of its deletion on the contractility, the energetics, and the respiration of the isolated perfused heart and characterized the response to low-flow ischemia and reperfusion with glucose and pyruvate as substrates. alpha(2)-AMPK deletion did not affect basal contractility, respiration, and high-energy phosphate contents but induced a twofold reduction in glycogen content and a threefold reduction in glucose uptake. Low-flow ischemia increased AMPK phosphorylation and stimulated glucose uptake and phosphorylation in both alpha(2)-knockout (alpha(2)-KO) and wild-type (WT) groups. The high sensitivity of alpha(2)-KO to the development of ischemic contracture was attributed to the constitutive impairment in glucose transport and glycogen content and not to a perturbation of the energy transfer by creatine kinase (CK). The functional coupling of MM-CK to myofibrillar ATPase and the CK fluxes were indeed similar in alpha(2)-KO and WT. Low-flow ischemia impaired CK flux by 50% in both strains, showing that alpha(2)-AMPK does not control CK activity. Despite the higher sensitivity to contracture, the postischemic contractility recovered to similar levels in both alpha(2)-KO and WT in the absence of fatty acids. In their presence, alpha(2)-AMPK deletion also accelerated the contracture but delayed postischemic contractile recovery. In conclusion, alpha(2)-AMPK is required for a normal glucose uptake and glycogen content, which protects the heart from the development of the ischemic contracture, but not for contractile recovery in the absence of fatty acids. |
| Databáze: | OpenAIRE |
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