Role of amp-activated protein kinase (AMPK) in myocardial ischemia-reperfusion (Is-Rs): differential effects depending on the energetic substrates available.

REZNIK, FEDERICO JOAQUIN; FELLET, ANDREA; FERNANDEZ PAZOS, MARIA DE LAS MERCEDES; VELEZ, DEBORA; VARELA, ALICIA; HERMANN, ROMINA; MESTRE CORDERO, VICTORIA; MARINA PRENDES, MARIA GABRIELA

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

AMPK functions as a cellular fuel gauge, being activatedto reestablish energy homeostasis at a cell-autonomous level. Therole of AMPK in myocardial Is-Rs remains uncertain.In this study, we explored the effects of the pharmacological inhibitionof AMPK by Compound C (CC; 10 μM) in isolated rat left atriasubjected to 75 min Is-75 min Rs. Since levels of fatty acids are elevatedin most clinical situations of Is-Rs, the influence of palmitatewas also studied. For this aim, atria were incubated in Krebs?Ringercontaining 10 mM glucose (G) or G and 1,2 mM palmitate (P), 95%O2?5% CO2, pH 7,4. For Is, the incubation medium contained 10 mM2-deoxy-D-glucose, 95% N2 ? 5% CO2, pH 6,8. ANOVA, n=8.Results showed a significant increase in AMPK endogenous activationduring Is, remaining activated during Rs. CC prevented it.During Is, peak contracture developed earlier in the atria stabilizedwith P. In this condition, CC increased maximum contracture. Theseresults were consistent with changes in tissue ATP content. Lactateaccumulation was reduced by P and even more by CC in both metabolicgroups. At the end of Rs contractile reserve (CR) attenuationwas more pronounced by P. CC showed dual effect, it increased CRattenuation in the presence of G, but reversed the harmful effectof P. These results were accompanied by similar changes in tissueATP content, but the rate of mitochondrial ATP synthesis showed nosignificant differences between groups. PDH activity was reduced inthe presence of P. CC reduced PDH activity in the atria incubatedwith G, but partially reverted P effect. CC also reduced autophagosomelike structures and LC3-II/LC3-I ratio, an established indicatorof autophagy, in both metabolic conditions. Cellular viability was notaffected by P or CC.The results support that intrinsic activation of AMPK has cardioprotectiveeffects in the reperfused atria when G is the only availableenergy substrate, but results deleterious when P is also available.