Effects of toxic doses of glutamate on Cu-Zn and Mn/superoxide dismutases activities in human glioma cell lines.

Recent research has implicated glutamate in the growth and invasive migration of gliomas. Superoxide dismutase (SOD) is involved in excitotoxicity and may influence cellular proliferative status. Thus, this study investigated the effects of gliotoxic doses of glutamate on Cu-Zn and Mn/SODs activities in human glioma cell lines. To this end, glioma cell lines (U87MG, U138MG and U251MG) were treated with glutamate (5-200 mM) during 48 h. Then, cell viability assays, clonogenic assay and Cu-Zn and Mn/SODs activities of the cell lines were performed. IC50values of glutamate were similar for both U87MG and U138MG cells (56 and 69 mM, respectively), while a higher value was detected for U251MG cells (110 mM). In the long term, 14 days after glutamate was removed from the culture media, cells showed partial or complete recovery. The effects of glutamate treatment on Cu-Zn and Mn/SODs activities varied among the distinct cell lines. While acute treatment with toxic doses of glutamate caused a significant decrease in the Cu-Zn/SOD activity of U138MG and U251MG cells, it did not affect Cu-Zn/SOD activity in U87MG cells. Only in U251MG cells, acute glutamate treatment decreased significantly Mn/SOD activity. In the long term (14 days after the 48 h treatment), glutamate did not affect either Cu-Zn or Mn/SODs activities. Thus, it may be suggested that SOD vulnerability to glutamate-mediated effects may be related to distinct tumoral cell behavior.