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Differential effects of AMP-activated protein kinase in isolated rat atria subjected to simulated ischemia–reperfusion depending on the energetic substrates available

  • Molecular and cellular mechanisms of disease
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Abstract

AMP-activated protein kinase (AMPK) is a serine–threonine kinase that functions primarily as a metabolic sensor to coordinate anabolic and catabolic processes in the cell, via phosphorylation of multiple proteins involved in metabolic pathways, aimed to re-establish energy homeostasis at a cell-autonomous level. Myocardial ischemia and reperfusion represents a metabolic stress situation for myocytes. Whether AMPK plays a critical role in the metabolic and functional responses involved in these conditions remains uncertain. In this study, in order to gain a deeper insight into the role of endogenous AMPK activation during myocardial ischemia and reperfusion, we explored the effects of the pharmacological inhibition of AMPK on contractile function rat, contractile reserve, tissue lactate production, tissue ATP content, and cellular viability. For this aim, isolated atria subjected to simulated 75 min ischemia–75 min reperfusion (Is-Rs) in the presence or absence of the pharmacological inhibitor of AMPK (compound C) were used. Since in most clinical situations of ischemia–reperfusion the heart is exposed to high levels of fatty acids, the influence of palmitate present in the incubation medium was also investigated. The present results suggest that AMPK activity significantly increases during Is, remaining activated during Rs. The results support that intrinsic activation of AMPK has functional protective effects in the reperfused atria when glucose is the only available energetic substrate whereas it is deleterious when palmitate is also available. Cellular viability was not affected by either of these conditions.

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Funding

This research was supported by grants from the University of Buenos Aires (UBACyT 20020130100309BA) and the Institute of Drug Chemistry and Metabolism (IQUIMEFA-CONICET).

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Authors and Affiliations

  1. Physiology Unit, Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Junín, 956, Buenos Aires, Argentina

    Romina Hermann, Victoria Evangelina Mestre Cordero, María de las Mercedes Fernández Pazos, Federico Joaquín Reznik, Débora Elisabet Vélez, Enrique Alberto Savino, María Gabriela Marina Prendes & Alicia Varela

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  1. Romina Hermann
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  2. Victoria Evangelina Mestre Cordero
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  3. María de las Mercedes Fernández Pazos
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Correspondence to Romina Hermann.

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Hermann, R., Mestre Cordero, V.E., Fernández Pazos, M.d.l.M. et al. Differential effects of AMP-activated protein kinase in isolated rat atria subjected to simulated ischemia–reperfusion depending on the energetic substrates available. Pflugers Arch - Eur J Physiol 470, 367–383 (2018). https://doi.org/10.1007/s00424-017-2075-y

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  • DOI: https://doi.org/10.1007/s00424-017-2075-y

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