CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
Autor/es:
BECERRA R; MARIANGELO JIE; DONOSO P; MUNDIÑA - WEILENMANN C; ROMAN B; SALAS M; SCHINELLA G; SAID M; DI CARLO MN; SANCHEZ G; VITTONE L
Lugar:
Buenos Aires
Reunión:
Congreso; XXII World Congress of the International Society for Heart Research (ISHR); 2016
Institución organizadora:
International Society for Heart Research (ISHR)
Resumen:
Background: Previous results from our laboratory showed that phosphorylation of ryanodine receptor-2 (RyR2) by Ca-calmodulin-dependent kinase II (CaMKII) was critical but not the unique event responsible for ventricular arrhythmias following ischemia/reperfusion (I/R). Oxidative stress is a prominent feature of I/R injury and both, CaMKII and RyR2 are subject to oxidation. Aim: The present study was designed to elucidate the contribution of redox changes in CaMKII and RyR2 on reperfusion arrhythmias. Methods: Isolated perfused rat hearts were subjected to I/R (20/30min) in the presence or absence of inhibitors of NADPH oxidase (Apocynin) and nitric oxide synthase (L-Name) and a free radical scavenger (MPG). Contractile and electrical parameters were recorded to detect ventricular premature beats (VPBs). CaMKII oxidation and S-nitrosylation, S-glutathionylation and free thiol levels (mBB) of RyR2 were assessed together with glutathione content (GSH) and ROS production (DHE).Results: CaMKII was oxidized in early reperfusion but this modification had no consequences in enzyme activity or RyR2 phosphorylation. In addition, I/R induced an increase in the reversible RyR2 oxidations: S-glutathionylation and S-nitrosylation. Accordingly, free thiols on RyR2 decreased. Pre-treatment with Apocynin and L-Name selectively abolished S-glutathionylation and S-nitrosylation of RyR2, respectively, and increased VPBs in I/R: (I/R: 44±14, Apocynin: 58±6 and L-Name: 64±16 VPBs, p
rds']