Mechanism of 1-Methyl-4-Phenylpyridinium-Induced Dopamine Release from PC12 Cells

被引：0
作者：
Jaturaporn Chagkutip
Piyarat Govitrapong
Sirirat Klongpanichpak
Manuchair Ebadi
机构：
[1] University of North Dakota School of Medicine and Health Sciences,Departments of Pharmacology and of Neurosciences
[2] Mahidol University,Neuro
[3] Mahidol University,Behavioural Biology Center, Institute of Science and Technology for Research and Development
[4] University of North Dakota,Center for Neuroscience and Department of Pharmacology, Faculty of Science
来源：
Neurochemical Research | 2005年 / 30卷
关键词：
MPP; selegiline; MAO-B inhibitor; tyrosine phosphorylation; synaptophysin; exocytosis; reactive oxygen species; Parkinson’s disease;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The molecular mechanism of 1-methyl-4-phenylpyridinium (MPP+), a Parkinsonism-inducing neurotoxin, has been studied in PC12 cells. The cells treated with MPP+ (100 μM) induced a rapid increase in phosphorylation of tyrosine residues of several proteins, including synaptophysin, a major 38 kDa synaptic vesicle protein implicated in exocytosis. An accelerated release of dopamine by MPP+ correlated with phosphorylation of synaptophysin. Exposing the cells to MPP+ triggered reactive oxygen species (ROS) generation within 60 min of treatment and the said effect was blocked by mazindol, a dopamine uptake blocker. In addition, pretreatment with 50–100 μM of selegiline, a selective MAO-B inhibitor, significantly suppressed MPP+-mediated ROS generation. These effects of MPP+ result in the generation of ROS, which may be involved in neuronal degeneration seen in Parkinson’s disease.
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页码：633 / 639
页数：6
相关论文
共 125 条
[1]  
Lotharius J.(2000)The parkinsonism-inducing drug 1-methyl-4 phenylpyridinium triggers intracellular dopamine oxidation. A novel machanism of toxicity J. Biol. Chem. 275 38581-38588
[2]  
O’Malley K. L.(1999)HEK-293 cells expressing the human dopamine transporter are susceptible to low concentrations of 1-methyl-4-phenylpyridinium (MPP Neurochem. Int. 35 393-403
[3]  
Storch A.(1986)) via impairment of energy metabolism Biochem. Biophys. Res. Commun. 134 743-748
[4]  
Ludolph A. C.(2001)Uptake of the neurotoxin MPP Brain Res. 905 199-206
[5]  
Schwarz J.(1985) by mitochondria and its relation to the inhibition of the mitochondrial oxidation of NAD Proc. Natl. Acad. Sci. 82 2173-2177
[6]  
Ramsay R. R.(1997)-linked substrates by MPP J. Neurochem. 69 1322-1325
[7]  
Salach J.(1998)Toxic effects of MPP Neuroscience 84 1177-1185
[8]  
Singer T. P.(1986) and MPTP in PC12 cells independent of reactive oxygen species formation Brain Res. 368 134-140
[9]  
Fonck C.(2001)Parkinsonism inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite 1-methyl-4-phenyl-pyridine by dopamine neurons explains selective toxicity Neurochem Int. 39 253-260
[10]  
Baudry M.(2001)Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter Biol. Signals Recept. 10 224-253
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