S-nitrosation ameliorates homocysteine-induced neurotoxicity and calcium responses in primary culture of rat cortical neurons

Homocyteine (HC)induces neurotoxicity through overstimulation of N-methyl-D-aspartate (NMDA) receptors in cortical neurons. Due to its high reactivity, the sulfhydryl group of HC may react with nitric oxide (NO). In the present study S-nitrosation decreased the homocysteine-evoked LDH releases from rat cortical neuronal cultures. Like HC, S-nitrosohomocysteine increased the intracellular calcium concentration ([Ca2+](i)) via NMDA receptor. However, S-nitrosohomocysteine was much less efficacious than HC for the increase of [Ca2+](i). Elevation of the glycine concentration to 50 mu M significantly increased tf-ie maximal calcium response of S-nitroso homocyteine, but not high enough to match that of HC in the presence of the same concentration of glycine. S-nitrosohomocysteine partially decreased the NMDA calcium responses in the presence of 1 and 50 mu M glycine, at least in part via the redox-modulatory site(s) of the NMDA receptor. These data indicate that NO ameliorates the potential, adverse properties of HC via S-nitrosylation in the pathogenesis of hyperhomocysteinemia. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.