title: 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: 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.
authors.affiliation: Institute of Cardiovascular Physiopathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, JE Uriburu 950 - 2nd floor, 1114, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Perez
authors.affiliation: Institute of Cardiovascular Physiopathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, JE Uriburu 950 - 2nd floor, 1114, Buenos Aires, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: D Annunzio
authors.affiliation: Institute of Cardiovascular Physiopathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, JE Uriburu 950 - 2nd floor, 1114, Buenos Aires, Argentina.
authors.forename: Tamara
authors.initials: T
authors.lastname: Mazo
authors.affiliation: Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Timoteo
authors.initials: T
authors.lastname: Marchini
authors.affiliation: Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Caceres
authors.affiliation: Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Evelson
authors.affiliation: Institute of Cardiovascular Physiopathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, JE Uriburu 950 - 2nd floor, 1114, Buenos Aires, Argentina. rgelpi@fmed.uba.ar.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gelpi
mesh_terms: D000367:Age Factors; D000818:Animals; D057775:Ischemic Postconditioning; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D013879:Thioredoxins
keywords: Aging; Ischemic postconditioning; Myocardial infarction; Thioredoxin-1