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


CONCLUSIONS
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+.
Yao
Hong-hong
HH
Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, China.
Ding
Jian-hua
JH
He
Hai-rong
HR
Hu
Gang
G
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000401:mortality / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015655:1-Methyl-4-phenylpyridinium