β-synuclein对Ⅱ型囊泡单胺转移体表达的促进作用

doi:10.6040/j.issn.1671-7554.0.2014.641

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

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. 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. 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

摘要/Abstract

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

杨璐, 周英泽, 倪明, 樊秀双, 满建梅, 郭军堂. β-synuclein对Ⅱ型囊泡单胺转移体表达的促进作用[J]. 山东大学学报（医学版）, 2015, 53(4): 61-64.

YANG Lu, ZHOU Yingze, NI Ming, FAN Xiushuang, MAN Jianmei, GUO Juntang. Beta-synuclein promotes the expression of vesicular monoamine transporter-2[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 61-64.

参考文献

[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.

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β-synuclein对Ⅱ型囊泡单胺转移体表达的促进作用

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

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