INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Mitochondrial NOS activity and hydrogen peroxide steady-state concentration during liver development in the rat.
Autor/es:
CARRERAS MC; CONVERSO D; LEVISMAN D; FINOCCHIETTO P; PODEROSO JJ
Lugar:
París, Francia
Reunión:
Congreso; XIth Bienal Meeting of the Society for Free Radical Research International; 2002
Institución organizadora:
Society for Free Radical Research International
Resumen:
Nitric oxide (NO) produced by mitochondrial NO synthase (mtNOS) is involved in the regulation of oxygen consumption and reactive oxygen species production. Considering that new evidences indicate that hydrogen peroxide (H2O2) participate in the regulation of cell cycle, the aim of this study was to evaluate liver mtNOS activity and H2O2 cytosolic steady-state level during the development of Wistar rats from 2-90 days. Purified mitochondria from newborn rats (P2-3) showed significantly lower mtNOS activity (19±2 vs 31±2 pmoles [3H]-L-citrulline/min/mg protein) and expression than adult organelles at day 30th. In accord, newborn mitochondria exhibited about 30% of maximal H2O2 production rate of adult organelles and lower complex enzyme activities. Accordingly, mtNOS activity correlated with MnSOD activity (r2: 0.73, p<0.05). Most of the mitochondrial-produced hydrogen peroxide can diffuse to cytosol where it is metabolized by glutathion peroxidase and catalase. In this setting, we calculated cell H2O2 steady-state level by measuring the ratio between NO-dependent H2O2 production rate (the difference of H2O2 production rate in the presence of L-arginine and plus L-arginine and L-NG-methyl-L-arginine), and the activities of the involved antioxidants enzymes. On this basis, the calculated H2O2 steady-state concentrations of early postnatal rats appeared to be decreased by one order of magnitude respect to adults (0.5 x 10-10 vs 0.7 x 10-9M, p<0.05). This fact was associated to increased liver proliferation as shown by increased cyclin D1 expression in liver homogenates of newborn rats. These data suggest that modulation of H2O2 and NO steady-state level by mtNOS activity contributes to redox-dependent regulation of cell cycle from proliferative to quiescent phases of development.