Mechanism of 1-Methyl-4-Phenylpyridinium-Induced Dopamine Release from PC12 Cells |
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| Authors: | Jaturaporn Chagkutip Piyarat Govitrapong Sirirat Klongpanichpak Manuchair Ebadi |
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| Institution: | (1) Departments of Pharmacology and of Neurosciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202, USA;(2) Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, 73170, Nakornpathom, Thailand;(3) Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, 10400 Bangkok, Thailand;(4) FACCP, Chester Fritz Distinguished Professor of Pharmacology and of Clinical Neurosciences, Associate Vice President for Medical Research, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, 58203 Grand Forks, ND, USA |
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| Abstract: | 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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| Keywords: | MPP+ selegiline MAO-B inhibitor tyrosine phosphorylation synaptophysin exocytosis reactive oxygen species Parkinson’ s disease |
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