CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ROLE OF P38MAPK ON THE EFFECTS OF NA+-HCO3- CO-TRANSPORTER AND CARBONIC ANHYDRASE BLOCKADE ON MITOCHONDRIAL POSTISCHEMIC ALTERATIONS: COMPARISON TO ACID REPERFUSION
Autor/es:
ALEJANDRO E AIELLO; ALEJANDRO CIOCCI PARDO; ÁLVAREZ BERNARDO VICTOR; LUISA F GONZÁLEZ ARBELÁEZ; SUSANA M MOSCA
Lugar:
Río de Janeiro
Reunión:
Congreso; IUPS 38th WORD CONGRESS; 2017
Institución organizadora:
Brazilian Society of Physiology
Resumen:
During ischemic period the increase of anaerobic glycolysis results in intracellular acidosis. The activation of alkalizing mechanisms, including the Na+-HCO3- co-transporter (NBC) which is associated to carbonic anhydrase (CA), leads to intracellular Na+ and Ca2+ increase. These events are critical determinants of reperfusion injury. Our objective was to determine the effects of NBC and CA blockade on mitochondrial alterations subsequent to myocardial ischemia-reperfusion. Isolated rat hearts were submitted after 20-min stabilization to the following protocols: 1.Non ischemic control (NIC): 90 min of perfusion; 2.Ischemic control (IC): 30 min of global ischemia (GI) and 60 min of reperfusion (R); 3.AR: an acid solution (pH=6.4) was infused during the first 3 min of R; 4.BZ: the CA inhibitor benzolamide (5 μM) was administered during the initial 10 min of R; 5.AL3: an antibody against extracellular loop 3 (AL3) of electrogenic NBC was applied during the first 10 min of R. To examine the participation of p38MAPK, all the interventions were performed in presence of p38MAPK inhibitor SB202190 (10 μM). Infarct size (IS) and postischemic recovery of myocardial function were measured. The expression of phospho-p38MAPK and proteins implicated in fission/fusion (Ser637Drp1, Mnf2 and OPA1) was evaluated. In isolated mitochondria membrane potential (m), Ca2+-mediated response and Ca2+ retention capacity were determined. AR, BZ and AL3 significantly decreased the IS and improved the post-ischemic recovery of contractility in comparison to IC. The content of p-p38MAPK and Ser637Drp1 at the end of R increased in all interventions. A normalization of m (-148±6, -146±5, -147±4 vs -95 ± 6 mV), a greater Ca2+ 200M-mediated response and retention capacity (1.3±0.1, 1.3±0.2, 1.3±0.1 vs 0.3±0.1; 412±34, 468±50, 466±47 vs 5±1nmol/mg prot) were detected when hearts were intervened. In presence of SB202190, the effects of AR, BZ and AL3 were partially attenuated. The present data demonstrate that CA and NBC blockade, similarly to AR, exert beneficial effects on ischemia-reperfusion injury through a p38MAPK activation-dependent mitochondrial state and dynamic improved. An attenuation of Ca2+ overload derived from a delay of pH normalization during R could be the mechanism BZ and AL3-mediated cardioprotection.