CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Dissecting the relevance of the SR-sites posphorylated by Ca2+- calmodulin kinase II (CaMKII) during ischemia reperfusion (I/R)
DI CARLO MN; VALVERDE CA; SAID M; MATTIAZZI A; SALAS M
Congreso; XX Annual Meeting of the International Society for Heart Research Latin American Section; 2012
International Society for Heart Research
Activation of CaMKII exerts a deleterious effect in the irreversible I/R. CaMKII inhibitors lead to significant decrease of infarct size, necrosisand apoptosis and improve contractility after I/R (Vila-Petroff et al.,2008). SR CaMKII-dependent phosphorylations are involved in themechanismof injury (Salas et al., 2010). Aim: to elucidate which of thetwo SR- sites phosphorylated by CaMKII: Thr17 of phospholamban(PLN), or Ser 2814 of RyR2, was responsible for the deleterious effect ofI/R. Experiments were performed in two strains of transgenic mice inwhich either Ser2814 of RyR2 or Thr17 and Ser16 of PLN,were mutatedto alanine (Ser2814A and DM, respectively). Isolated Langendorffperfused hearts were submitted to global I/R (45/120 min). Comparingwith their controls, DM hearts showed an increase in the infarct area(Ctrl: 20.8±4.4% vs. DM: 44.8±10.7%) together with impairedcontractile recovery (DM: 44.9±3.5% of control). In contrast,Ser2814A hearts had a significant reduction in the infarct area (Ctrl:32.1±4.9 % vs. Ser2814A: 16.4±1.6 %, n=6)) with an improvementin contractility (Ctrl: 2.13±0.49% vs. Ser2814A: 7.66±2.01% of pre-I), and diminished left ventricular end diastolic pressure during both Iand R. Conclusion: 1. CaMKII dependent PLN phosphorylation isbeneficial for the post-infarct recovery; 2. CaMKII dependent RyR2phosphorylation, participates in the deleterious cascade possibly byincreasing SR Ca2+ leak during diastole.