Inhibition of vesicular monoamine transporter-2 activity in α-synuclein stably transfected SH-SY5Y cells

被引：76

作者：

Guo, Jun Tang ^{[1
,2
]}

Chen, An Qi ^{[1
,3
]}

Kong, Qi ^{[1
]}

Zhu, Hua ^{[1
]}

Ma, Chun Mei ^{[1
]}

Qin, Chuan ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Inst Lab Anim Sci, Beijing 100021, Peoples R China

[2] Weifang Med Coll, Dept Pathophysiol, Weifang 261042, Shandong, Peoples R China

[3] Weifang Med Coll, Dept Pathol, Weifang 261042, Shandong, Peoples R China

来源：

CELLULAR AND MOLECULAR NEUROBIOLOGY | 2008年 / 28卷 / 01期

关键词：

synuclein; vesicular monoamine transporter-2; Parkinson's disease; reactive oxygen species; dopamine uptake;

D O I：

10.1007/s10571-007-9227-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 [H-3] 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.

引用

页码：35 / 47

页数：13

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