上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

组蛋白去乙酰化酶6对帕金森病细胞模型中α-突触核蛋白阳性包涵体的作用

王飞1,2，杜芸兰2，李焰生1,2   

  1. 上海交通大学 医学院 1.附属仁济医院南院神经内科， 上海 201112； 2.附属仁济医院神经内科， 上海 200127
  • 出版日期:2015-12-28 发布日期:2016-01-21
  • 通讯作者: 李焰生, 电子信箱: lliyans@hotmail.com。
  • 作者简介:王飞（1988—）， 女， 住院医师， 硕士; 电子信箱: wangfei667788@126.com。
  • 基金资助:

    国家自然科学基金青年基金（81000538）。

Effects of histone deacetylase 6 on α-synuclein-positive inclusion bodies in the cell model of Parkinson's disease

WANG Fei1,2, DU Yun-lan2, LI Yan-sheng1,2   

  1. 1.Department of Neurology, Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China; 2.Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2015-12-28 Published:2016-01-21
  • Supported by:

    Young Scientists Project of National Natural Science Foundation of China， 81000538

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摘要：

目的  研究帕金森病（PD）细胞模型中组蛋白去乙酰化酶6（HDAC6）的表达水平及其对α-突触核蛋白阳性包涵体的影响。方法  使用Lipofectamin 2000构建稳定过表达野生型α-突触核蛋白的人神经母细胞瘤SK-N-SH细胞，并加入蛋白酶体抑制剂lactacystin制作α-突触核蛋白异常聚集的PD模型；采用Western blotting检测HDAC6的表达水平；使用HDAC6特异性抑制剂tubacin处理后，免疫荧光染色检测α-突触核蛋白阳性的包涵体水平。结果  Lactacystin处理细胞的HDAC6表达水平较对照细胞明显升高，且α-突触核蛋白阳性的包涵体增多，而经tubacin处理后包涵体减少，差异均有统计学意义（P<0.05）。结论  在蛋白酶体抑制剂制作的PD细胞模型中，抑制升高的HDAC6可使α-突触核蛋白阳性的包涵体水平降低；其机制可能与HDAC6参与α-突触核蛋白从寡聚体向包涵体形式的转化从而起保护作用有关。

关键词: 帕金森病；组蛋白去乙酰化酶6；&alpha, -突触核蛋白；包涵体

Abstract:

Objective  To investigate the expression of histone deacetylase 6 (HDAC6) and its effects on α-synuclein-positive inclusion bodies in the cell model of Parkinson's disease (PD). Methods  The human neuroblastoma cells SK-N-SH with stable over-expressed wild type α-synuclein were constructed via Lipofectamin 2000. The PD model with abnormal aggregation of α-synuclein was established by adding the proteasome inhibitor lactacystin. The expression of HDAC6 was detected by Western blotting. After being treated with HDAC6 specific inhibitor tubacin, the level of α-synuclein-positive inclusion bodies was detected by immunofluorescence staining. Results  Compared with the controls, the expression of HDAC6 of lactacystin-treated cells was significant higher and α-synuclein-positive inclusion bodies were more. Treatment by tubacin reduced the amount of inclusion bodies and the difference was statistically significant (P＜0.05). Conclusion  In the PD cell model established by proteasome inhibitor, inhibition of increased HDAC6 can reduce the amount of α-synuclein-positive inclusion bodies, which may be relevant to the involvement of HDAC6 in the conversion of α-synuclein from oligomers to inclusion bodies, so as to play a role of protection.

Key words: Parkinson's disease, histone deacetylase 6, α-synuclein, inclusion body