期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

抑制组蛋白去乙酰化酶6对帕金森病细胞模型中α-突触核蛋白寡聚体的影响 被引量：1

在线阅读 下载PDF
导出
摘要 目的研究帕金森病(Parkinson's disease,PD)细胞模型中抑制组蛋白去乙酰化酶6(histone deacet ylase 6,HDAC6)对α-突触核蛋白寡聚体的影响及可能机制。方法将野生型pcDNA3.1-α-突触核蛋白真核表达质粒稳定转染人神经母细胞瘤SK-N-SH细胞,并加入蛋白酶体抑制剂lactacystin制作异常蛋白质聚集的PD模型;用不同浓度的选择性HDAC6抑制剂tubacin处理细胞24 h后,使用噻唑蓝比色法检测细胞存活率,蛋白免疫印迹法检测α-突触核蛋白寡聚体、热休克蛋白70(heat shock protein 70,HSP70)及HSP27表达水平。结果 Lactacystin组较对照组的细胞存活率降低(P<0.05)、寡聚体水平升高(P<0.05)、HSP70及HSP27的表达水平升高(P<0.05);Tubacin处理后的lactacystin组细胞存活率进一步降低(P<0.05)、寡聚体水平进一步升高(P<0.05)、而HSP70和HSP27表达水平降低(P<0.05)。结论 在蛋白酶体抑制剂制作的PD细胞模型中,抑制HDAC6可使细胞存活率降低、α-突触核蛋白寡聚体水平升高,其机制可能与HSP70和HSP27表达水平的降低有关。
作者 王飞 杜芸兰 卫立辛 李焰生
机构地区 上海交通大学医学院附属仁济医院神经内科 上海交通大学医学院附属仁济医院中心实验室
出处 《中国神经精神疾病杂志》 CAS CSCD 北大核心 2013年第5期304-307,共4页 Chinese Journal of Nervous and Mental Diseases
基金 国家自然科学基金资助项目(编号:81000538)
关键词 帕金森病 组蛋白去乙酰化酶6α-突触核蛋白 寡聚体 热休克蛋白
分类号 R742.5 [医药卫生—神经病学与精神病学]
  • 相关文献

参考文献10

  • 1Soper JH, Kehm V, Burd CG, et al. Aggregation of α-synuclein in S. cerevisiae is associated with defects in endosomal trafficking and phospholipid biosynthesis[J]. J Mo! Neurosci. 2011, 43 (3): 391-405.
  • 2Du G, Liu X, Chen X, et al. Drosophila histone deacetylase 6 protects dopaminergic neurons against c--synuclein toxicity by promoting inclusion formation[J]. Mol Biol Cell, 2010, 21(13): 2128-2137.
  • 3Emadi S, Kasturirangan S, Wang MS, et al. Detecting morphologically distinct oligomeric forms of alpha-synuclein[J]. J Biol Chem, 2009, 284(17): 11048-11058.
  • 4杨旭,杨云鹏,马英,周长青,张玉平,陈中美,彭国光.pVAX1-IL4/SYN-B核酸疫苗对鱼藤酮慢性帕金森病小鼠的治疗作用[J].中国神经精神疾病杂志,2012,38(2):87-91. 被引量：3
  • 5张国华,徐杰,吴达荣,陶恩祥.利福平对鱼藤酮诱导大鼠的抗多巴胺神经元凋亡作用[J].中国神经精神疾病杂志,2012,38(1):10-13. 被引量：3
  • 6Klucken J, Shin Y, Masliah E, et al. Hsp70 reduces alpha-synuclein aggregation and toxicity[J]. J Biol Chem. 2004, 279(24): 25497-25502.
  • 7Zourlidou A, Payne Smith MD, Latchman DS. HSP27 but not HSP70 has a potent protective effect against alpha-synuclein-induced cell death in mammalian neuronal cells[J]. J Neurochem. 2004, 88(6):1439-1448.
  • 8Chen S, Owens GC, Makarenkova H,et al. HDAC6 regulates mitochondrial transport in hippocampal neurons[J]. PLoS One, 2010, 5(5): e10848.
  • 9Dompierre JP, Godin JD, Charrin BC, et al. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulinacetylation[J]. J Neurosci, 2007, 27(13): 3571-3583.
  • 10Su M, Shi JJ, Yang YP, et al. HDAC6 regulates aggresome-autophagy degradation pathway of α-synuclein in response to MPP*-induced stress[J]. J Neurochem. 2011, 117(1): 112-120.

二级参考文献25

  • 1何卿玮,王加才,彭国光,王法祥.pVAX1-IL-4/SYN-B融合质粒的构建及表达[J].免疫学杂志,2009,25(5):588-590. 被引量：8
  • 2Amer DA,Irvine CB,El-Agnaf OM.Inhibitors of alpha-synu-clein oligomerization and toxicity:a future therapeutic strategy for Parkin-son s disease and related disoiders[J].Exp Brain Res,2006,173(2):223-233.
  • 3Kawai H,Makino Y,Hirobe M,et al.Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives:uptake by dopamine transporter and activity to induce parkinsonism[J].J Neurochem,1998,70(2):745-751.
  • 4Masliah E,Rockenstein E,Adame A,et al.Effects of alpha-synuclein immunization in a mouse model of Parkinson's dis-ease[J].Neuron,2005,46(6):857-868.
  • 5Bohlen und Halbach Ov,Schober A,Krieglstein Genes.Pro-teins,and neurotoxins involved in Parkinson's disease[J].Progress in Neurobiology,2004,73(3):151-77.
  • 6Fearnley JM,Lees AJ.Ageing and Parkinson's disease:sub-stantia nigra regional selectivity[J].Brain,1991,114(5):2283-2301.
  • 7Tomiyama T,Shoji A,Kataoka K.Inhibition of amyloid β pro-tein aggregation and neurotoxicity by rifampicin[J].J.Biol.Chem,1996,271(12):6839-6845.
  • 8Xu J,Wei C,Xu C,et al.Rifampicin protects PC12 cells a-gainst MPP+-induced apoptosis and inhibits the expression of an α-Synuclein multimer[J].Brain Res,2007,1139(3):220-225.
  • 9Ziv I,Melamed E,Nardi N,et al.Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons-a possible novel pathogenetic mechanism in Parkinson's disease[J].Neu-rosci Lett,1994,170(1):136-140.
  • 10Volles MJ,Lansbury PT Jr.Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkin-son's disease[J].Biochemistry,2003,42(26):7871-7878.

共引文献4

同被引文献13

  • 1Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy [J]. CancerLett, 2008, 269(1): 7-17.
  • 2Chen PS, Wang CC, Bortner CD, et al. Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity[J]. Neuroscience, 2007, 149(1) : 203 -212.
  • 3Su M, Shi JJ, Yang YP, et al. HDAC6 regulates aggresome-autophagy degradation pathway of cL-synuclein in response to MPP -induced stress[J]. JNeurochem, 2011, 117(1): 112-120.
  • 4Du G, Liu X, Chen X, et al. Drosophila histone deaeetylase 6 protects dopaminergic neurons against c-synuelein toxicity by promoting inclusion formation[ Jl. Mol Biol Cell, 2010, 21 ( 13 ) : 2128 -2137.
  • 5Ding H, Dolan PJ, Johnson GV. Histonc deaeetylase 6 interacts with the microtubule-associated protein tau[J]. J Neurochem, 2008, 106(5) : 2119 -2130.
  • 6Kawaguchi Y, Kovacs JJ, McLaurin A, et al. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress [ J ]. Cell, 2003, 115 (6) : 727 -738.
  • 7Du Y, Wang F, Zou J, et al. Histone deacetylase 6 regulates cytotoxic c-synuclein accumulation through induction of the heat shock response [ J]. Neurobiol Aging, 2014, 35 (10) : 2316 - 2328.
  • 8Simes-Pires C, Zwick V, Nurisso A, et al. HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs? [J] Mol Neurodegener, 2013, 8(5): 7.
  • 9Simms-Waldrip T, Rodriguez-Gonzalez A, Lin T, et al. The aggre- some pathway as a target for therapy in hematologic malignancies [J]. Mol Genet Metab, 2008, 94(3): 283 -286.
  • 10Miki Y, Mori F, Tanji K, et al. Accumulation of histone deacetylase 6, an aggresome-related protein, is specific to Lewy bodies and glial cytoplasmic inclusions [ J ]. Neuropathology, 2011, 31 (6) : 561 - 568.

引证文献1

二级引证文献1

中国神经精神疾病杂志
2013年 第5期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部