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

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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: 3 month-old), middle-aged (MA: 12 month-old), and old (O: 20 month-old) mice were used. Langendorff-perfused hearts were subjected to 30 min of ischemia and 120 min of reperfusion (I/R group). After ischemia, we performed 6 cycles of R/I (10 s each) followed by 120 min 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.

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Funding

This study was funded by the University of Buenos Aires UBACYT# 20020110100159 and the National Agency for Technological and Scientific Promotion: PICT 0373.

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Authors and Affiliations

  1. Institute of Cardiovascular Physiopathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, JE Uriburu 950 – 2nd floor, 1114, Buenos Aires, Argentina

    Virginia Perez, Verónica D´Annunzio, Tamara Mazo & Ricardo J. Gelpi

  2. Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Timoteo Marchini, Lourdes Caceres & Pablo Evelson

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  1. Virginia Perez
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  2. Verónica D´Annunzio
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Correspondence to Ricardo J. Gelpi.

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All procedures performed in these studies involving animals were in accordance with the ethical standards of the Animal Care and Research Committee of the University of Buenos Aires (CICUAL UBA # 0037016/2012).

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Perez, V., D´Annunzio, V., Mazo, T. et al. Ischemic postconditioning confers cardioprotection and prevents reduction of Trx-1 in young mice, but not in middle-aged and old mice. Mol Cell Biochem 415, 67–76 (2016). https://doi.org/10.1007/s11010-016-2677-2

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