Sensitive and insensitive states of cultured glioma cells to glutamate damage.
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.
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D005910:Glioma / Q000648:ultrastructure*; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D006854:Hydrocortisone / Q000494:pharmacology; D009410:Nerve Degeneration / Q000187:drug effects*; D051381:Rats
D005971:Glutamates; D015074:2-Aminoadipic Acid; D018698:Glutamic Acid; D003994:Bucladesine; D006854:Hydrocortisone