Sensitive and insensitive states of cultured glioma cells to glutamate damage

Autor: Sachiko Hatakenaka, Satoru Kato, Koroku Negishi, Yoshihiro Higuchi, Haruhiro Higashida
Rok vydání: 1984
Předmět:
Zdroj: Brain research. 303(2)
ISSN: 0006-8993
Popis: 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 μM 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.
Databáze: OpenAIRE