INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Relative amounts of NO and ubiquinol determine mitochondrial protein nitration in endotoxemia.
Autor/es:
LISDERO, C, SCHÖPFER, F, RIOBÓ, N, CARRERAS, MC, BOCZKOWSKI, J, PODEROSO, JJ
Lugar:
Estocolmo, Suecia
Reunión:
Congreso; 6th International Meeting, Biology of Nitric Oxide.; 1999
Institución organizadora:
NO Society
Resumen:
We have recently described that, in endotoxemia, iNOS promotes the production of O2 reactive species in diaphragm mitochondria, leading to the formation of peroxynitrite (ONOO-) and protein nitration. As production of O2 species and ONOO- steady state involves the reaction of NO and ONOO- with reduced mitochondrial ubiquinol (UQ), the aim of this study was to assess whether iNOS-dependent nitration of mitochondrial proteins and function is affected by UQ content in different target organs. Mitochondria from liver, heart, diaphragm and lung were studied 6 h after E. coli LPS inoculation (10mg/kg). iNOS expression and  activity were determined and respiratory control ratios (RCR) and hydrogen peroxide production were measured as parameters of mitochondrial function. Mitochondrial protein nitration was assessed by Western blot. Nitration patterns were shown to correlate with mitochondrial dysfunction. Respiratory controls decreased by about 30-50 % in mitochondria from liver and diaphragm which had intensely nitrated mitochondrial proteins but not in heart which contains the highest amount of UQ and, accordingly, showed the lowest degree of protein nitration. Lung mitochondria which contain the lowest concentration of UQ neither produced detectable H2O2 production nor showed protein nitration. These results propose that the ratio between iNOS activity and available UQ could determine the degree of protein nitration and the associated mitochondrial dysfunction and suggest that, UQ protects from oxidative damage produced by high concentrations of NO.