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

作　　者：Hong-hongYAO Jian-huaDING Hai-rongHE GangHU 

机构地区：[1]DepartmentofPharmacologyandNeurobiology,NanjingMedicalUniversity,Nanjing210029,China

出　　处：《Acta Pharmacologica Sinica》2004年第7期855-860,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China (No 39970846) and Natural Science Foundation of Jiangsu Educational Council (No03KJB310086 and No99KJB350001 ).

摘　　要：AIM: To investigate the effect of 1-methyl-4-phenylpyridinium (MPP^+) on theglutamate uptake into cultured C6 glioma cells. METHODS: The glutamate uptake into C6 glioma cellswas measured by radio-ligand binding assay method. The effect of MPP^+ on the morphology of C6glioma cells was observed under phase contrast microscopy; apoptosis of C6 glioma cells weremeasured by FITC-labeled Annexin V staining and flow cytometry. Cell viability was measured by MTTmethod. RESULTS: MPP^+ inhibited glutamate uptake into C6 glioma cells. However, MPP^+ failed toinduce any morphological changes of C6 glioma cells, and exposure to MPP^+ had no effect on theviability 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 uptakeand completely reversed MPP^+-induced inhibitory effect on glutamate uptake. CONCLUSION: The presentresults indicate that glutamate transporters may have important pathogenetic implications inParkinson disease. MPP^+-induced inhibition of glutamate uptake was due to the dysfunction ofglutamate transporters; TPA enhanced glutamate uptake and completely reversed the inhibitory effectof MPP^+.AIM: To investigate the effect of 1-methyl-4-phenylpyridinium (MPP^+) on theglutamate uptake into cultured C6 glioma cells. METHODS: The glutamate uptake into C6 glioma cellswas measured by radio-ligand binding assay method. The effect of MPP^+ on the morphology of C6glioma cells was observed under phase contrast microscopy; apoptosis of C6 glioma cells weremeasured by FITC-labeled Annexin V staining and flow cytometry. Cell viability was measured by MTTmethod. RESULTS: MPP^+ inhibited glutamate uptake into C6 glioma cells. However, MPP^+ failed toinduce any morphological changes of C6 glioma cells, and exposure to MPP^+ had no effect on theviability 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 uptakeand completely reversed MPP^+-induced inhibitory effect on glutamate uptake. CONCLUSION: The presentresults indicate that glutamate transporters may have important pathogenetic implications inParkinson disease. MPP^+-induced inhibition of glutamate uptake was due to the dysfunction ofglutamate transporters; TPA enhanced glutamate uptake and completely reversed the inhibitory effectof MPP^+.

关 键 词：1-METHYL-4-PHENYLPYRIDINIUM glutamate acid glioma apoptosis 4-O-methyl-12-O-tetradecanoyl- phorbol-13-acetate 

分 类 号：R741[医药卫生—神经病学与精神病学]