Inhibitory effects of 1-methyl-4-phenylpyridinium on glutamate uptake into cultured C6 glioma cells.

AIM: To investigate the effect of 1-methyl-4-phenylpyridinium (MPP+) on the glutamate uptake into cultured C6 glioma cells. METHODS: The glutamate uptake into C6 glioma cells was measured by radio-ligand binding assay method. The effect of MPP+ on the morphology of C6 glioma cells was observed under phase contrast microscopy; apoptosis of C6 glioma cells were measured by FITC-labeled Annexin V staining and flow cytometry. Cell viability was measured by MTT method. RESULTS: MPP+ inhibited glutamate uptake into C6 glioma cells. However, MPP+ failed to induce any morphological changes of C6 glioma cells, and exposure to MPP+ had no effect on the viability and the apoptotic percentage of C6 glioma cells. Incubation with 12-O-tetradecanoylphorbol -13-acetate (TPA), a protein kinase C activator, caused a significant increase in glutamate uptake and completely reversed MPP+-induced inhibitory effect on glutamate uptake. CONCLUSION: The present results indicate that glutamate transporters may have important pathogenetic implications in Parkinson disease. MPP(+)-induced inhibition of glutamate uptake was due to the dysfunction of glutamate transporters; TPA enhanced glutamate uptake and completely reversed the inhibitory effect of MPP+.