THIOREDOXIN-1 IS INVOLVED IN CARDIOPROTECTION CONFERRED BY ISCHEMIC POSTCONDITIONING

PEREZ VIRGINIA; D´ ANNUNZIO VERÓNICA; MAZO TAMARA; MARCHINI TIMOTEO; CACERES LOURDES; EVELSON PABLO; GELPI RICARDO

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA-V CONGRESO NACIONAL DE LA ASOCIACIÓN ARGENTINA DE CIENCIA Y TECNOLOGÍA DE ANIMALES DE LABORATORIO; 2016

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Thioredoxin-1 (Trx1) maintains the cellular redox status anddecreases the infarct size in ischemia/reperfusion injury (I/R).However, it is not fully understood the role of Trx1 in ischemicpostconditioning (PostC). The aim was to study if Trx1 is involvedin the PostC cardioprotection mechanism.Wild type mice hearts (Wt), transgenic mice hearts overexpressingTrx1, and a dominant negative (DN-Trx1) mutant (C32S/C35S) of Trx1 were used. The mice hearts were subjected to 30min of I and 120 of R (Langendorff technique) (I/R group). In thePostC group, after I, a protocol of 6 cycles of R/I (15 sec and 10sec each), was performed. The assessment of the infarct sizewas performed using TTC. Reduced (GSH) and oxidized (GSSG)glutathione levels were measured by HPLC and Trx, pAkt andpGSK3beta expression were evaluated by western blot. Data areexpressed as mean ± SEM and p<0.05 was considered statisticallysignificant. n= 6 each goup.The infarct size in the Wt-PostC group decreased in comparisonto the Wt-I/R group (54.6±2.4 vs 40.0±2.1%, p<0.05), but this protectionwas abolished in DN-Trx1-PostC (47.7±1.1%). The Trx1-I/Rand PostC reduced infarct size at the same magnitude (35.9±2.1and 38.4±1.3%, respectively, p<0.05 vs. Wt-I/R). After I/R, the Trx1expression decreased in Wt (0.32±0.09 AUDO). However, the PostCpreserved the Trx1 expression (0.65±0.08 AUDO, p<0.05 vs. WtI/R),meanwhile DN-Trx1-PostC did not preserved Trx1 levels. InWt-PostC, I/R-Trx1 and PostC-Trx1 increased Akt and GSK3betaphosphorylation compared to Wt-I/R, without changes in DN-Trx1groups. In conclusion, Trx1 plays a key role in the PostC protectionmechanism, since when this protein is inactive the cardioprotectivemechanism was abolished. Given that the cardioprotection conferby both, Trx1 overexpression and PostC, is through the activationof Akt/GSK3beta cell survival pathway, no synergic effect wasevidenced between both protection mechanisms