title: Inhibition of vesicular monoamine transporter-2 activity in alpha-synuclein stably transfected SH-SY5Y cells.
abstract: alpha-Synuclein plays a key role in the pathological neurodegeneration in Parkinson's disease. Although its contribution to normal physiology remains elusive, the selective degeneration of alpha-synuclein-containing dopaminergic neurons in Parkinson's disease may be linked to abnormal alpha-synuclein induced toxicity. In the present study, a complex of alpha-synuclein and vesicular monoamine transporter-2 was identified by GST-Pull Down experiment. In wild-type alpha-synuclein stably transfected SH-SY5Y cell lines, the activity of vesicular monoamine transporter-2 decreased by 31% as determined by [(3)H] dopamine uptake, and its expression also decreased in both protein and mRNA levels using western and northern blot analysis. Overexpression of wild-type alpha-synuclein did not induce cell death or apoptosis, but significantly enhanced the intracellular reactive oxygen species level as assayed by flow cytometry. These data suggest that Up-regulated alpha-synuclein expression inhibits the activity of vesicular monoamine transporter-2, thereby interrupting dopamine homeostasis and resulting in dopaminergic neuron injury in Parkinson's disease.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, 5 Panjiayuannanli, Beijing, 100021, China.
authors.forename: Jun Tang
authors.initials: JT
authors.lastname: Guo
authors.forename: An Qi
authors.initials: AQ
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Kong
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Chun Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D006690:Bisbenzimidazole / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; D006690:Bisbenzimidazole; D004298:Dopamine