Physiopathological Effects of the NO Donor 3-Morpholinosydnonimine on Rat Cortical Synaptosomes

The NO donor 3-Morpholinosydnonimine (SIN-1) releases NO in the presence of molecular oxygen. In this study, we evaluated the effect of SIN-1 on mitochondria of rat cortical synaptosomes. We demonstrated in vitro that the amount of ONOO- generated and H2O2 formation directly correlated with SIN-1 concentration. The mean oxygen consumption by synaptosomal mitochondria was approximately 3.8 nmol of O2 min -1 mg-1 protein, which decreased significantly in the presence of SIN-1 1 mM to 2.5 nmol O2 min-1 mg -1. This decrease was not modified by catalase or Trolox, demonstrating that ONOO- was responsible for the effect. The same concentration of SIN-1 caused a significant decrease of ATP production by synaptosomal mitochondria and depolarized the mitochondrial membrane. Moreover, ROS production increased progressively and was completely inhibited by pre-incubation of synaptosomes with Trolox. Finally, phosphatidylserine was externalized and, at the same time, intrasynaptosomal lactate dehydrogenase decreased confirming both, the external membrane breakdown after the addition of SIN-1 and the damage to the synaptosomes. © 2008 Springer Science+Business Media, LLC.