INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Modulation of liver mitochondrial nitric oxide synthase (mtNOS) and cellular redox metabolism by the thyroid status
Autor/es:
FRANCO MC; ANTICO ARCIUCH V; PERALTA JG; PODEROSO JJ; CARRERAS MC
Lugar:
Buenos Aires
Reunión:
Congreso; XII Biennial Meeting of the Society for Free Radical Research International; 2004
Institución organizadora:
Society for Free Radical Research International
Resumen:
Basal metabolic rate and cellular proliferation are regulated by thyroid status, and nitric oxide (NO) produced by mtNOS is a modulator of mitochondrial respiration and cellular redox metabolism. The reciprocity between these effects was analysed in male Wistar rats: with hypothyroidism (methimazole 0.02%, 4 wk), hypothyroidism+T3 (15 µgT3/kg.day IP, 3 days) and hyperthyroidism (60 µgT3/kg.day IP, 3 days). Plasma TSH was >80 ng/ml in hypothyroidism and decreased by 55% in hyperthyroidism (controls: 12±3 ng/ml; p<0.05). Liver mtNOS activity increased by 52% in hypothyroidism, and decreased by 44% in hyperthyroidism (controls: 52±19 pmoles citrulline/mg prot.min; p<0.05). Similar pattern was observed in mtNOS mRNA and protein levels. NO-dependent H2O2 steady state concentration (+ L-arginine) decreased by 60% in hyperthyroidism (control: 0.10±0.04x10-9M; p<0.05). In hypothyroidism, nitration of mitochondrial proteins was indicative of peroxynitrite formation. The p38-MAPK activity resulted 74% higher in hypothyroidism and 42% lower in hyperthyroidism, respect to controls; the opposite was observed in ERK-1/2 activation. Expression of cyclin-D1 mRNA and protein was 50% lower in hypothyroidism and 60% higher in hyperthyroidism, respect to controls. These results suggest that thyroid status regulates cell redox metabolism and subsequently the differential activation of MAPKs and cell cycle proteins through the modulation of mtNOS content.