THE CARDIOPROTECTION MEDIATED BY ISCHEMIC POSTCONDITIONING AND TRX1 OVEREXPRESSION RESTORE MITOCHONDRIAL FUNCTION IN MICE HEART.

PEREZ, MARÍA VIRGINIA; GOMEZ ANABELA; MAZO TAMARA; VICO, TAMARA ANTONELA; VANASCO, VIRGINIA; ZAOBORNYJ TAMARA; CORRALES AYELEN; CASANOVA VERÓNICA; CICALE ELIANA; GRECCO CARLA; ALVAREZ, SILVIA; DANNUNZIO, VERÓNICA; GELPI RICARDO J

Mar de Plata

Congreso; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2019; 2019

Abstract/Resumen: Thioredoxin-1 (Trx1) maintains the cellular redox status and decreases the infarct size in ischemia/reperfusion injury (I/R). However, it is not fully understood the role of Trx1in ischemic postconditioning (PostC) in young and middle-aged mice and its relation with mitochondrial function. The aim was to study if Trx1is involved in the PostC cardioprotection mechanism and can restore mitochondrial function and if the age can modify this. Wild type mice hearts (Wt), transgenic mice hearts overexpressing Trx1, and a dominant negative mutant (DN-Trx1) of Trx1 were used, mice were divided in young group (4 months) and middle-aged group (12 months). The mice hearts were subjected to 30 min of I and 120 min of R (Langendorff technique) (I/R group). In the PostC group, after I, a protocol of 6 cycles of R/I was performed. The assessment of the infarct size was performed using TTC. Also, it was measure mitochondrial function (polarographically with a Clark-type electrode). Data are expressed as mean±SEM, n= 6 each group and p<0.05 was considered statistically significant. Previously, we showed that Trx1 is involved in cardioprotection conferred by PostC in young mice but in middle-aged mice, the cardioprotection was abolished in groups with PostC. This infarct size behaviour was accompanied by a lack of survival proteins phosphorylation (Akt and GSK3B) and changes in Trx1 expression (in Wt group). Trx1 activity was diminished, H2O2 production and protein nitration were increased in all middle-aged groups. Our results showed that Trx1 plays a key role in the PostC protection mechanism in young mice but in middle-aged mice, this cardioprotective mechanism was abolished. Recently, we performed the same groups and observed no changes in state 4 oxygen uptake in middle-aged mice and young mice neither. In young groups, state 3 oxygen uptake was significantly lower in Wt-I/R group than Wt-Nx group (Wt-Nx: 137.4 ± 6.0 vs. Wt-I/R: 97.1 ± 14.2) and in Wt-PostC group the value tended to recover normoxic values (113.9 ± 11.7). In middle-aged groups, state 3 oxygen uptake was lower in Wt-I/R and Wt-PostC groups than Wt-Nx group (Wt-Nx: 176.0 ± 9.4 vs. Wt-I/R: 135.5 ± 9.6 and Wt-PostC: 113.9 ± 11.7). No differences appeared between Trx1 groups and the same was observed in DN-Trx1 groups. In conclusion, we found the cardioprotection mediated by PostC and Trx1 overexpression restore mitochondrial function in young mice but not in middle-aged mice.