Oxido nítrico sintasa neuronal y función mitocondrial.

CZERNICYNIEC, A.; BUSTAMANTE, J.; LORES ARNAIZ, S.

Mar del Plata

Congreso; Congreso Conjunto de Sociedades Biomédicas: SAIC-SAI-SAFE-SABiología-SABiofísicaSAN-SAF; 2004

Sociedades Biomédicas: SAIC-SAI-SAFE-SABiología-SABiofísicaSAN-SAF

Deprenyl, a known inhibitor of monoamine oxidase B (MAO B), may generate changes in nitric oxide (NO) production and in mitochondrial function. The aim of this work was to determine in vivo and in vitro effects of deprenyl on nitric oxide synthase (NOS) activity in different brain subcellular fractions and on mitochondrial function. MAO activity was also measured. For in vivo studies, 13-months Swiss mice were injected with deprenyl (20 mg/kg) and sacrificed after 1.5 hours. For in vitro assays, brain mitochondria, synaptosomes and cytosol were incubated with different deprenyl concentrations and NOS activity was measured. The effect of deprenyl on O2 consumption and H2O2 production was studied in intact mitochondria. MAO activity was also measured in submitochondrial membranes (SMP). Deprenyl treatment produced a 45 % inhibition in brain SMP NOS activity and a 51% increase in brain mitochondrial oxygen uptake (state 3). Moreover, inhibition of MAO activity (55%) produced a decrease in mitochondrial H2O2 production (46%) in deprenyl-treated animals. Deprenyl inhibited MAO in vitro in all concentration range, although at levels greater than 5 uM, no significant changes occur in the amount of the inhibition. Incubation with deprenyl at concentrations that can inhibit MAO, also inhibits NOS activity in mitochondrial, synaptosomal and cytosolic fractions in a concentration dependent manner. Our results show that deprenyl can modify NOS activity and mitochondrial function. These actions together with MAO inhibition may contribute to neuroprotector effects of the drug.