INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Mitochondrial nitric oxide synthase and redox signaling in rat liver development
Autor/es:
CARRERAS MC; CONVERSO DP; LEVISMAN D; LORENTI A; BARBICH M; PODEROSO JJ
Lugar:
Cádiz, España
Reunión:
Congreso; Meeting of the Oxygen Club of California; 2003
Institución organizadora:
Oxygen Club of California
Resumen:
In the last years, different mitochondrial nitric oxide synthase isoforms have been described in rat and mouse tissues such as liver, skeletal muscle and, more recently, heart and brain. The regulation of mtNOS results in the modulation of oxygen uptake and reactive oxygen species production which in turn may regulate the activity of cell cycle regulatory proteins determining proliferation or cell cycle arrest. The aim of this study was to evaluate the modulation of liver mtNOS and the resultant hydrogen peroxide steady-state concentration during rat liver development and a possible relation to proliferative and quiescent cell stages. In this study, the embryonic days 17 and 19 of gestation and postnatal day 2 represent proliferative hepatocyte phenotype and  postnatal 15 to 90 the quiescent phenotype. MtNOS was almost undetectable in fetal liver and progressively increased after birth up to adult levels at P30. NO-dependent mitochondrial H2O2 production and Mn-SOD paralleled the developmental modulation of mtNOS activity. Proliferative hepatocyte phenotypes showed higher phospho-ERK1/2 and cyclin D1 expression and lower phospho-p38 MAPK expression while quiescent phenotypes showed an opposite pattern. Treatment of P2 isolated hepatocytes with NO and H2O2 level modulators resulted in changes in [3H] thymidine incorporation. The present results suggest that modulation of NO and H2O2 steady-state concentrations during liver development contributes to regulate MAP kinase activities and cyclin D1 expression leading to proliferation or cell cycle arrest.