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 μM significantly increased the maximal calcium response of S- nitrosohomocyteine, 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 I and 50 μM 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.
- N-methyl-D-aspartate receptor
- [Ca](i), glycine
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