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 H(2)O(2) formation directly correlated with SIN-1 concentration. The mean oxygen consumption by synaptosomal mitochondria was approximately 3.8 nmol of O(2) min(-1) mg(-1) protein, which decreased significantly in the presence of SIN-1 1 mM to 2.5 nmol O(2) 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.
Department of Physiology, University of Siena, Siena, Italy.
J
J
Blanco Garcia
C
C
Aldinucci
S M
SM
Maiorca
M
M
Palmi
M
M
Valoti
G
G
Buonocore
G P
GP
Pessina
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000648:ultrastructure; D002839:Chromans / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D030421:Peroxynitrous Acid / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014867:Water / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D020030:Nitric Oxide Donors; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014867:Water; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002385:linsidomine; D000255:Adenosine Triphosphate; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid