[Cytotoxicity of excitatory sulfur amino acids in primary cultured rat cerebral neurons].
The elevation of taurine level in the central nervous system of patients with amyotrophic lateral sclerosis (ALS) indicates the presence of derangement in sulfur amino acid metabolism in this disease. In the metabolic pathway from methionine to taurine and in its branch pathways, excitatory sulfur amino acids are formed. These are cysteine (Cys), cysteine sulfinic acid (CSA), cysteic acid (CA), homocysteine sulfinic acid (HCSA), homocysteic acid (HCA) and S-sulfo cysteine (SC). This study was undertaken to investigate whether these excitatory sulfur amino acids have any cytotoxicity, since excitotoxicity has recently been implicated in the pathogenesis of ALS. Primary cultures of cerebral neurons were prepared from fetal rats, using an established method. Neuronal cell injury was assessed by examination of cultures with phase-contrast microscopy and with bright-field examination of trypan blue staining, a dye staining non-viable cells. The morphological estimate of cell injury was confirmed by the measurement of the activity of lactate dehydrogenase, released from damaged or destroyed cells, in the extracellular fluid. This convenient and quantitative index invariably correlated with the morphological estimates. Among the 6 sulfur amino acids, CSA and HCSA showed cytotoxicity, while Cys, CA, HCA and SC did not. K0.5 of CSA was 80 microM, and that of HCSA was 300 microM. The cytotoxicity of CSA was stronger than that of glutamate, K0.5 of which was 100 microM. Relevance of these excitotoxic sulfur amino acids, especially CSA to the pathogenesis of ALS has not been studied. This possibility will be a subject for future study.
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First Department of Internal Medicine, Kyorin University School of Medicine.
D000603:Amino Acids, Sulfur / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D018846:Excitatory Amino Acids / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000603:Amino Acids, Sulfur; D018846:Excitatory Amino Acids