INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Congenital hypothyroidism modulates mitochondrial nitric oxide and redox balance, shifting apoptotic pattern during post-natal rat brain development.
Autor/es:
Y. ALIPPE1, M.E. ELGUERO, H. PÉREZ, M.C. CARRERAS, J.J. PODEROSO
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:
Previously, we demonstrated that mitochondrial localization and activity of neuronal nitric oxide synthase (nNOS) are regulated by thyroid hormones. Here, we evaluated the role of mitochondrial NO as a secondary messenger during post-natal brain development under hypothyroidism. Congenital hypothyroidism was induced by methimazole treatment in pregnant rats and pups at 5-15 and 30 post-natal days were analyzed. nNOS expression and activity were both maximally increased in mitochondria of hypothyroid group (H) at P15, according to NO levels measured by flow cytometry (DAF-FM). As a result, Complex I (CI) activity was significantly inhibited in hypothyroidism at P5 and P15 stages, and it was recovered to control group (C) values by pumping infusion of L-NAME (30mg/Kg/day) from postnatal day 10 to 15. CI inhibition led to a 3.2-fold increase of superoxide anion and H2O2 levels in P15 of H, respect to C and L-NAME group, that was in parallel to a higher expression of mitochondrial Bax. TUNEL assay showed increased apoptosis at P30H that was prevented by L-NAME. We conclude that inhibition of nNOS activity during critical neonatal period in hypothyroidism, reestablished mitochondrial metabolism and redox status, altered by increased NO production, which allowed to restoring apoptotic balance in immature brain.