IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
PHYSIOLOGICAL REGULATION OF HEART MITOCHONDRIAL NITRIC OXIDE SYNTHASE
Autor/es:
VALDEZ LB; ZAOBORNYJ T; BOMBICINO SS; BOVERIS A
Lugar:
Montevideo, Uruguay
Reunión:
Congreso; V Meeting of the South American Group of the Society for Free Radical Biology and Medicine; 2007
Institución organizadora:
Society for Free Radical Biology and Medicine
Resumen:
Heart submitochondrial membranes produce NO at a rate of 2.2±0.1 nmol/min.mg protein; and this production accounts for 60% of total cellular NO generation. NO production has been observed not only in mitochondrial membranes but also in coupled mitochondria, being NO release 40% lower in state 3 than in state 4. NO release from heart mitochondria shows an exponential dependence on mitochondrial membrane potential, being this dependence more important in the physiological range of membrane potential. The ability of mtNOS activity to modulate mitochondrial O2 uptake and H2O2 production, by its product NO, is termed mtNOS functional activity. Changes in mtNOS functional activity reflect variations in mitochondrial NO production and [NO]ss. Supplementation of state 3 heart mitochondria with 5 mM L-arg decreased the respiration rate by 15-20%, while supplementation of the mitochondrial preparation with 5-10 mM L-NAME increased O2 consumption by 10%. Pre-incubation of heart cubes with 10 mM L-arg produced a 40% decrease in O2 consumption, while the addition of 10-20 mM L-NAME did not modified O2 uptake. Concerning H2O2 production, the addition of 1 mM L-arg enhanced H2O2 production by 15-20% in heart mitochondria in state 4, whereas the supplementation of the preparation with 5 mM L-NAME declined H2O2 generation by 10%. Pre-incubation of heart cubes with 10 mM L-arginine increased 4-times [H2O2]ss, while the supplementation of the tissue incubation medium with 20 mM L-NAME abolished H2O2 signal in the reaction medium. To conclude, the fact that heart mitochondrial NO production accounts for about 60% of total cellular NO generation, and that heart mtNOS is a highly regulated enzyme under physiological, pathological and pharmacological situations, makes evident the central role of mitochondrial NO in cardiomyocytes.