INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Antioxidant protection of thioredoxin-1 (trx1) in heart of septic mice
Autor/es:
SANCHEZ-VILLAMIL JP;FINOCCHIETTO P; D´ANNUNZIO V; GELPI RJ. PODEROSO JJ; CARRERAS M
Lugar:
Buenos Aires
Reunión:
Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine-South American Group; 2013
Institución organizadora:
Society for free Radical Biology and Medicina-South American Group
Resumen:
  In sepsis-induced myocardial dysfunction, oxidative stress is an underlying cause1. Increase evidence suggests the mainly role of trx1 in oxidative stress regulation2. The objective was to evaluate its protective mechanism in mitochondrial function and cardiac contractility.   METHODS Transgenic male mice with trx1 cardiac-specific overexpression (trx1 k-in) and its wildtype (wt), 12 - 20 weeks old, were subjected to cecal ligation and double puncture (21G needle) or sham operation. Survival rate was determined. After 6, 18 or 24 h, activity of antioxidant enzymes, protein carbonylation, respiratory chain complexes activity and mitochondrial hydrogen peroxide (H2O2) production were evaluated. Inotropism was estimated as left ventricular developed pressure (LVDP) and contractile reserve after β-adrenergic stimulus through addition of isoproterenol (ISO) (1 uM) by the Lagendorff technique.   RESULTS Trx1 improved average life expectancy (trx1 k-in: 36, wt: 28 h; p=0.0204) LVDP values before β-adrenergic stimulus were similar, but trx1 showed better response to ISO at 6 h (wt: 5,6 ± 1,39; trx1k-in: 14,9 ± 1,39 mmHg p=0.0012). In trx1k-in, trx1 activity was significantly higher by sepsis time, MnSOD activity increased up to 24 h while it was decreased in wt, and complex II-III activity was inhibited later.  Protein oxidation was lower in trx1k-in and linked to mitochondrial H2O2  production.   CONCLUSIONS Trx1 attenuated the drop in contractile reserve at 6 h and delayed mitochondrial oxidative damage in sepsis-induced myocardial