Cellular and Molecular Neurobiology

, Volume 28, Issue 1, pp 35–47

Inhibition of Vesicular Monoamine Transporter-2 Activity in α-Synuclein Stably Transfected SH-SY5Y Cells

  • Jun Tang Guo
  • An Qi Chen
  • Qi Kong
  • Hua Zhu
  • Chun Mei Ma
  • Chuan Qin
Original Paper

DOI: 10.1007/s10571-007-9227-0

Cite this article as:
Guo, J.T., Chen, A.Q., Kong, Q. et al. Cell Mol Neurobiol (2008) 28: 35. doi:10.1007/s10571-007-9227-0

Abstract

α-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 α-synuclein-containing dopaminergic neurons in Parkinson’s disease may be linked to abnormal α-synuclein induced toxicity. In the present study, a complex of α-synuclein and vesicular monoamine transporter-2 was identified by GST-Pull Down experiment. In wild-type α-synuclein stably transfected SH-SY5Y cell lines, the activity of vesicular monoamine transporter-2 decreased by 31% as determined by [3H] dopamine uptake, and its expression also decreased in both protein and mRNA levels using western and northern blot analysis. Overexpression of wild-type α-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 α-synuclein expression inhibits the activity of vesicular monoamine transporter-2, thereby interrupting dopamine homeostasis and resulting in dopaminergic neuron injury in Parkinson’s disease.

Keywords

Synuclein Vesicular monoamine transporter-2 Parkinson’s disease Reactive oxygen species Dopamine uptake 

Abbreviations

PD

Parkinson’s disease

VMAT2

Vesicular monoamine transporter-2

ROS

Reactive oxygen species

TH

Tyrosine hydroxylase

DAT

Dopamine transporter

DA

Dopamine

PBS

Phosphate-buffered saline

PVDF

Polyvinylidene difluoride

MAO

Monoamine oxidase

MPTP

1-Methyl- 4-phenyl-1,2,3,6-tetrahydropyridine

MPP+

1-Methyl-4-phenylpyridinium

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jun Tang Guo
    • 1
    • 2
  • An Qi Chen
    • 1
    • 3
  • Qi Kong
    • 1
  • Hua Zhu
    • 1
  • Chun Mei Ma
    • 1
  • Chuan Qin
    • 1
  1. 1.Institute of Laboratory Animal SciencesChinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC)BeijingChina
  2. 2.Department of PathophysiologyWeifang Medical CollegeWeifangChina
  3. 3.Department of PathologyWeifang Medical CollegeWeifangChina

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