Ischemic postconditioning confers cardioprotection and prevents reduction of Trx-1 in young mice, but not in middle-aged and old mice.

Abstract

Thioredoxin-1 (Trx-1) is part of an antioxidant system that maintains the cell redox homeostasis but their role on ischemic postconditioning (PostC) is unknown. The aim of this work was to determine whether Trx-1 participates in the cardioprotective mechanism of PostC in young, middle-aged, and old mice. Male FVB young (Y: 3month-old), middle-aged (MA: 12month-old), and old (O: 20month-old) mice were used. Langendorff-perfused hearts were subjected to 30min of ischemia and 120min of reperfusion (I/R group). After ischemia, we performed 6 cycles of R/I (10s each) followed by 120min of reperfusion (PostC group). We measured the infarct size (triphenyltetrazolium); Trx-1, total and phosphorylated Akt, and GSK3β expression (Western blot); and the GSH/GSSG ratio (HPLC). PostC reduced the infarct size in young mice (I/R-Y: 52.3±2.4 vs. PostC-Y: 40.0±1.9, p<0.05), but this protection was abolished in the middle-aged and old mice groups. Trx-1 expression decreased after I/R, and the PostC prevented the protein degradation in young animals (I/R-Y: 1.05±0.1 vs. PostC-Y: 0.52±.0.07, p<0.05). These changes were accompanied by an improvement in the GSH/GSSG ratio (I/R-Y: 1.25±0.30 vs. PostC-Y: 7.10±2.10, p<0.05). However, no changes were observed in the middle-aged and old groups. Cytosolic Akt and GSK3β phosphorylation increased in the PostC compared with the I/R group only in young animals. Our results suggest that PostC prevents Trx-1 degradation, decreasing oxidative stress and allowing the activation of Akt and GSK3β to exert its cardioprotective effect. This protection mechanism is not activated in middle-aged and old animals.