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

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Abstract

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.

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Acknowledgements

This work was supported in part by PAR Progetti, Università di Siena and in part by MIUR PRIN 2005 Prot. 2005 06 9071-005

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Authors and Affiliations

  1. Department of Physiology, University of Siena, Via A. Moro, 53100, Siena, Italy

    J. Blanco Garcia, C. Aldinucci, S. M. Maiorca & G. P. Pessina

  2. Department of Biomedical Sciences, University of Siena, 53100, Siena, Italy

    M. Palmi & M. Valoti

  3. Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, 53100, Siena, Italy

    G. Buonocore

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  1. J. Blanco Garcia
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  2. C. Aldinucci
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  6. G. Buonocore
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  7. G. P. Pessina
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Correspondence to G. P. Pessina.

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Blanco Garcia, J., Aldinucci, C., Maiorca, S.M. et al. Physiopathological Effects of the NO Donor 3-Morpholinosydnonimine on Rat Cortical Synaptosomes. Neurochem Res 34, 931–941 (2009). https://doi.org/10.1007/s11064-008-9854-y

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  • DOI: https://doi.org/10.1007/s11064-008-9854-y

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