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 microM 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 1 and 50 microM 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.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000506:poisoning*; D007425:Intracellular Membranes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology