Research Papers: Gerotarget (Focus on Aging):
Loss of myocardial protection against myocardial infarction in middle-aged transgenic mice overexpressing cardiac thioredoxin-1
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Verónica D´Annunzio1,5,*, Virginia Perez1,*, Tamara Mazo1, Marina C. Muñoz2,5, Fernando P. Dominici2,5, María C. Carreras3,5, Juan José Poderoso3,5, Junichi Sadoshima4 and Ricardo J. Gelpi1,5
1 Institute of Cardiovascular Physiopathology and Department of Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina
2 Institute of Chemistry and Biological Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
3 Laboratory of Oxygen Metabolism, University Hospital, University of Buenos Aires, Buenos Aires, Argentina
4 Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
5 Member of the National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina
* These authors have contributed equally to this work
Ricardo J. Gelpi, email:
Keywords: myocardial infarction, ischemia/reperfusion, thioredoxin-1, middle-aged, Gerotarget
Received: December 21, 2015 Accepted: January 30, 2016 Published: February 25, 2016
Thioredoxin-1 (Trx1) protects the heart from ischemia/reperfusion (I/R) injury. Given that the age at which the first episode of coronary disease takes place has considerably decreased, life at middle-aged (MA) emerges as a new field of study. The aim was determine whether infarct size, Trx1 expression and activity, Akt and GSK-3β were altered in young (Y) and MA mice overexpressing cardiac Trx1, and in a dominant negative (DN-Trx1) mutant of Trx1. Langendorff-perfused hearts were subjected to 30 minutes of ischemia and 120 minutes of reperfusion (R). We used 3 and 12 month-old male of wild type (WT), Trx1, and DN-Trx1. Trx1 overexpression reduced infarct size in young mice (WT-Y: 46.8±4.1% vs. Trx1-Y: 27.6±3.5%, p < 0.05). Trx1 activity was reduced by 52.3±3.2% (p < 0.05) in Trx1-MA, accompanied by an increase in nitration by 17.5±0.9%, although Trx1 expression in transgenic mice was similar between young and middle-aged. The expression of p-Akt and p-GSK-3β increased during reperfusion in Trx1-Y. DN-Trx1 mice showed neither reduction in infarct size nor Akt and GSK-3β phosphorylation. Our data suggest that the lack of protection in Trx1 middle-aged mice even with normal Trx1 expression may be associated to decreased Trx1 activity, increased nitration and inhibition of p-Akt and p-GSK-3β.
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