CONICET | Buscador de Institutos y Recursos Humanos

Thioredoxin-1 maintains the cellular redox status and decreases the infarct size in ischemia/reperfusioninjury. However, whether the increase of thioredoxin-1 expression or its lack of activity modifies theprotection conferred by ischemic postconditioning has not been yet elucidated. The aim was to evaluateif the thioredoxin-1 overexpression enhances the posctconditioning protective effect, and whether thelack of the activity abolishes the reduction of the infarct size. Wild type mice hearts, transgenic micehearts overexpressing thioredoxin-1, and a dominant negative mutant (C32S/C35S) of thioredoxin-1were used. The hearts were subjected to 30 min of ischemia and 120 min of reperfusion (Langendorff)(I/R group) or to postconditioning protocol (PostC group). The infarct size in the Wt-PostC group decreasedin comparison to the Wt-I/R group (54.6 ± 2.4 vs. 39.2 ± 2.1%, p < 0.05), but this protection was abolishedin DN-Trx1-PostC group (49.7 ± 1.1%). The ischemia/reperfusion and postconditioning in mice overex-pressing thioredoxin-1 reduced infarct size at the same magnitude (35.9 ± 2.1 and 38.4 ± 1.3%, p < 0.05vs. Wt-I/R). In Wt-PostC, Trx1-I/R and Trx1- PostC, Akt and GSK3 phosphorylation increased comparedto Wt-I/R, without changes in DN-Trx1 groups. In conclusion, given that the cardioprotection conferredby thioredoxin-1 overexpression and postconditioning, is accomplished through the activation of theAkt/GSK3 survival pathway, no synergic effect was evidenced. Thioredoxin-1 plays a key role in the postconditioning, given that when this protein is inactive the cardioprotective mechanism was abol-ished. Thus, diverse comorbidities or situations modifying the thioredoxin activity, could explain theabsence of this strong mechanism of protection in different clinical situations.

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