La cardioprotección conferida por la tiorredoxina-1 se abole en la edad media de la vida involucrando la Akt y la Gsk-3beta

MAZO T; PEREZ V; GOMEZ A; LLAMOSAS C; NICOLOSI L; RUBIO MC; DANNUNZIO V; GELPI JR

Mar del Plata

Congreso; LIX Reunión científica anual de la Sociedad Argentina de Investigación Clínica; 2014

Introduction: Recent studies have demonstrated that thioredoxin-1 (Trx-1), a potent physiological antioxidant, protects the heart from ischemia/reperfusion (I/R) injury, prevents apoptosis and improves post- myocardial infarction (MI) cardiac function in young (y) mice. However, Trx-1 interacts with various signal transduction processes in myocardial I/R beyond its direct activity as an antioxidant. In this sense, it has been shown that Trx-1 overexpression induces Akt-signaling pathway during ischemic stress. Objectives: The present study was designed to determine whether Trx-1 expression and activity, as well as p-Akt, are altered in young and middle-aged (ma) transgenic (tg) mice overexpressing cardiac Trx-1, in a way that may contribute to increased susceptibility to myocardial I/R. Methods: Langendorff-perfused hearts were subjected to 30 minutes of global ischemia followed by 120 minutes of reperfusion. We used 3 and 12 month-old male wild type (wt) mice (wty, n=8 and wtma, n=7 respectively) and 3 and 12 month-old tg mice overexpressing cardiac Trx-1 (tgy, n=7 and tgma, n=6 respectively). Infarct size (TTC) was measured. Trx-1, Akt and p-Akt (ser 473) expression (western blot), Trx-1 activity (Insulin reduction assay), and nitration (western blot) were also measured. Results: Infarct size was 46.8±4.1 in wty, 52.6±5.2 in wtma, 27.3±3.5 in tgy (p