Abstract：
:Cytotoxic effects of L-glutamate and related compounds were investigated on rat glioma C6 cells in vitro. Within 12-24 h, addition of glutamate to the culture medium, resulted in degeneration of the C6 cells. The ED50 for glutamate-induced damage was about 4 mM. Seventeen structural analogues of glutamate, including agonists and antagonists for glutamate receptors as well as glutamate-uptake inhibitor, were examined concerning their toxicity on C6 cells. Among them, L-aminoadipic acid, DL-aminopimelic acid, DL-homocysteic acid, L-cysteic acid, quisqualic acid, L-glutamic acid diethyl ester and 2-amino-4-phosphonobutyric acid elicited similar degeneration at comparable concentrations. The D-isomer of glutamate was not cytotoxic. Following differentiation of C6 cells with 1 mM dibutyryl cyclic AMP or 3 mM sodium butyrate, they were no longer susceptible to L-glutamate and L-aminoadipate. C6 cells treated with 10 microM hydrocortisone, which is known to induce glutamine synthetase activity, were also resistant to L-glutamate, but not to L-aminoadipate. The decomposition of cellular DNA in glutamate-treated cultures was confirmed by flow cytometer analysis. The results demonstrate that the sensitivity of C6 cells to glutamate-induced cytotoxicity was modified by cellular metabolic conditions. This indicates that cultured glioma C6 cells are a useful model system to investigate the molecular mechanism of glutamate gliotoxicity in vitro.
journal_name
Brain Resjournal_title
Brain researchauthors
Kato S,Higashida H,Higuchi Y,Hatakenaka S,Negishi Kdoi
10.1016/0006-8993(84)91222-8subject
Has Abstractpub_date
1984-06-15 00:00:00pages
365-73issue
2eissn
0006-8993issn
1872-6240pii
0006-8993(84)91222-8journal_volume
303pub_type
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