您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (4): 61-64.doi: 10.6040/j.issn.1671-7554.0.2014.641

• 基础医学 • 上一篇    下一篇

β-synuclein对Ⅱ型囊泡单胺转移体表达的促进作用

杨璐1, 周英泽2, 倪明1, 樊秀双1, 满建梅1, 郭军堂1   

  1. 1. 潍坊医学院基础医学院病理生理学教研室, 山东 潍坊 261053;
    2. 四川省安岳县人民医院病理科, 四川 安岳 642350
  • 收稿日期:2014-09-24 修回日期:2014-12-24 出版日期:2015-04-10 发布日期:2015-04-10
  • 通讯作者: 郭军堂.E-mail:guojuntang@163.com E-mail:guojuntang@163.com
  • 基金资助:
    山东省自然科学基金(ZR2011HM014)

Beta-synuclein promotes the expression of vesicular monoamine transporter-2

YANG Lu1, ZHOU Yingze2, NI Ming1, FAN Xiushuang1, MAN Jianmei1, GUO Juntang1   

  1. 1. Department of Pathophysiology, School of Basic Medicine, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Pathology, Anyue County People's Hospital, Anyue 642350, Sichuan, China
  • Received:2014-09-24 Revised:2014-12-24 Online:2015-04-10 Published:2015-04-10

PDF (PC)

124

摘要： 目的 探讨β-突触核蛋白(β-synuclein)对Ⅱ型囊泡单胺转移体(VMAT2)表达的影响.方法 通过2',7'-二氯荧光黄双乙酸盐(DCFH-DA)染色检测β-synuclein稳定表达对细胞内ROS水平的影响;采用免疫荧光双标法、免疫组织化学法及Western blotting检测VMAT2在稳定转染β-synuclein 的SH-SY5Y细胞及正常SH-SY5Y细胞中的表达情况.结果 DCFH-DA荧光染色显示,稳定表达β-synuclein的细胞的荧光强度较正常SH-SY5Y细胞明显减弱.VMAT2在稳定转染β-synuclein 的SH-SY5Y细胞中的表达水平较正常SH-SY5Y细胞明显升高. 结论 β-synuclein能够促进VMAT2的表达,减少胞浆内DA含量,抑制ROS产生,在帕金森病多巴胺神经元变性过程中对其起到保护作用.

关键词: &beta, 活性氧类物质, 电休克, -突触核蛋白, 帕金森病, Ⅱ型囊泡单胺转移体, 木僵, 精神病

Abstract: Objective To investigate the effect of β-synuclein on the expression of vesicular monoamine transporter-2(VMAT2). Methods The effects of β-synuclein stable expression on the intracellular ROS level were detected by dichlorofluorescein diacetata(DCFH-DA). The expression of VMAT2 was detected by double immunofluorescence, immunohistochemistry and Western blotting in SH-SY5Y cells which were transfected stably with β-synuclein and normal SH-SY5Y cells. Results The intracellular ROS level in the cells stably expressing β-synuclein was significantly lower than that of normal SH-SY5Y cells.The expression of β-synuclein in the SH-SY5Y cells which were stably transfected with β-synuclein was higher than that of normal SH-SY5Y cells. Conclusion β-synuclein can reduce the content of DA in cytosolic by promoting the expression of VMAT2, which can inhibit the generation of ROS. It plays an important protective role in the process of dopamine neurons' degeneration in Parkinson's disease.

Key words: Beta-synuclein, Reactive oxygen species, Parkinson's, disease, Vesicular monoamine transporter-2

中图分类号: 

  • R741
[1] Bellucci A, Navarria L, Zaltieri M, et al.Alpha-synuclein synaptic pathology and its implications in the development of novel therapeutic approaches to cure Parkinson's disease[J]. Brain Res, 2012, 1432:95-113.
[2] Ruipérez V, Darios F, Davletov B. Alpha-synuclein, lipids and Parkinson's disease[J]. Prog Lipid Res, 2010, 49(4):420-428.
[3] Lam HA, Wu N, Cely I, et al. Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human α-Synuclein[J]. Neurosci Res, 2011, 89(7):1091-1102.
[4] Lohr KM, Bernstein AI, Stout KA, et al. Increased vesicular monoamine transporterenhances dopamine release and opposes Parkinson's disease-related neurodegeneration in vivo[J]. Proc Natl Acad Sci U S A, 2014, 111(27):9977-9982.
[5] Brighina L, Riva C, Bertola F, et al.Analysis of vesicular monoamine transporter2 polymorphisms in Parkinson's disease[J]. Neurobiol Aging, 2013, 34(6):1712.e9-13. doi:10.1016/j.neurobiolaging.2012.12.020.
[6] Guo JT, Chen AQ, Kong Q, et al. Inhibition of vesicular monoamine transporter-2 activity in alpha-synuclein stably transfected SH-SY5Y cells[J]. Cell Mol Neurobiol, 2008, 28(1):35-47.
[7] Yamin G, Munishkina LA, Karymov MA, et al. Forcing nonamyloidogenic beta-synuclein to fibrillate[J]. Biochemistry, 2005, 44(25):9096-9107.
[8] Cali T, Ottolini D, Negro A, et al. α-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions[J]. Biol Chem, 2012, 287(22):17914-17929.
[9] Nishioka K, Wider C, Vilario-Güell C, et al. Association of alpha-, beta-, and gamma-Synuclein with diffuse lewy body disease[J]. Arch Neurol, 2010, 67(8):970-975.
[10] 沈原,赵永波,刘功禄,等. α-突触核蛋白的表达与氧化应激水平的相互影响[J].中国神经免疫学和神经病学杂志, 2011, 18(3):174-177. SHEN Yuan, ZHAO Yongbo, LIU Gonglu, et al. The interaction between the oxidative stress level and α-synuclein protein expression[J].Chinese Journal of Neuroimmunology and Neurology, 2011, 18(3):174-177.
[11] Okamura N, Villemagne VL, Drago J, et al. In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with(18)F-AV-133[J]. Nucl Med, 2010, 51(2):223-228.
[12] Lotharius J, Barg S, Wiekop P, et al. Effect of mutant alpha-synuclein on dopamine-homeostasis in a new human mesencephalic cell line[J]. Biol Chem, 2002, 277(41):38884-38894.
[13] Giasson BI, Murray IV, Trojanowski JQ, et al. A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly[J]. Biol Chem, 2001, 276(4):2380-2386.
[14] Tabrizi SJ, Orth M, Wilkinson JM, et al. Expression of mutant alpha- synuclein causes inereased susceptibility to dopamine toxicity[J]. Hum Mol Genet, 2000, 9(18):2683-2689.
[1] 张莹 王宏伟 王慧 陈福琴. Graves病复发患者外周血中转化生长因子β1水平的变化[J]. 山东大学学报(医学版), 2209, 47(6): 80-.
[2] 朱晓冉,李秀华,任延红,毛飞,方雨晴,赵张宁,王雅琳,刘天淏,张艳青,韩润冬. 帕金森病患者抑郁对睡眠、认知功能的影响[J]. 山东大学学报 (医学版), 2025, 63(3): 63-70.
[3] 任延红,李秀华,朱晓冉,方雨晴,赵张宁,毛飞,王雅琳,张艳青,刘天淏,徐新荣. 艾地苯醌对帕金森病认知障碍患者的疗效[J]. 山东大学学报 (医学版), 2024, 62(10): 106-114.
[4] 张秀芳,李沛铮,张博涵,孙丛丛,刘艺鸣. 生长分化因子15在LPS诱导的帕金森病模型中的保护作用及机制[J]. 山东大学学报 (医学版), 2022, 60(5): 1-7.
[5] 赵海龙,王皓,方雨晴,毛飞,赵张宁,田祥奇,徐新荣,王敏,李秀华. 增服艾地苯醌对34例帕金森病抑郁患者的疗效观察[J]. 山东大学学报 (医学版), 2022, 60(4): 38-44.
[6] 刘丽雯,马俊,李沛铮,张秀芳,刘艺鸣. 128例帕金森病照料者负担及影响因素[J]. 山东大学学报 (医学版), 2022, 60(4): 45-49.
[7] 田祥奇,王皓,徐新荣,方雨晴,毛飞,赵张宁,赵海龙,吴丙云,李秀华. 超低频经颅磁刺激对帕金森病睡眠障碍患者的疗效观察[J]. 山东大学学报 (医学版), 2022, 60(12): 19-25.
[8] 李湘青,殷欣,赵雪莲,赵培庆. NK细胞亚群CD56bright在帕金森患者外周血中的表达及临床意义[J]. 山东大学学报 (医学版), 2021, 59(2): 34-40.
[9] 张晓韬,何天齐,朱梅佳,唐吉友,赵张宁,毛飞,方雨晴,刘小民,马高亭,张小雨,张霄,王敏,李秀华. 艾地苯醌联合治疗帕金森病疗效的临床观察[J]. 山东大学学报 (医学版), 2019, 57(4): 34-41.
[10] 郭配,李秀华,张晓韬,何天齐,朱梅佳,唐吉友,赵张宁,毛飞. 伴有睡眠障碍帕金森病患者的睡眠特征及其影响因素[J]. 山东大学学报 (医学版), 2018, 56(4): 76-80.
[11] 勾云, 周波, 魏操,陈运华, 徐利,刘芬, 张春林, 文敏. 硫辛酸对帕金森病大鼠黑质线粒体的保护作用[J]. 山东大学学报（医学版）, 2017, 55(8): 18-23.
[12] 崔萌,郑冀鲁,田思男,李连军,张琦,金讯波,王慕文. 前列腺绿激光汽化术治疗良性前列腺梗阻伴帕金森病的疗效[J]. 山东大学学报（医学版）, 2017, 55(7): 100-102.
[13] 马翔宇,李卫国,陈思,陈腾,李超,徐硕,徐淑军,李新钢. 山东大学齐鲁医院神经外科脑深部电刺激术手术步骤标准化操作流程(SOP)暨核查表[J]. 山东大学学报（医学版）, 2017, 55(5): 117-121.
[14] 张文君,沈遥遥,戴庭敏,柴艺轩,涂江龙. 帕金森病并发喉痉挛1例[J]. 山东大学学报（医学版）, 2017, 55(5): 125-126.
[15] 王思,李秀华,杜鹃,岳龙涛,王瑶,刘菲,郭配. 侧脑室注射腺病毒介导的GDNF基因对帕金森病的保护作用[J]. 山东大学学报（医学版）, 2016, 54(4): 32-36.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发