线粒体转录终止因子蛋白家族的表达以及在MPTP / MPP+ 诱导下的表达变化

张林冰 韩艳艳 仇石 许珊 左伋 刘雯

解剖学报 ›› 2017, Vol. 48 ›› Issue (1) : 19-24.

PDF(627 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(627 KB)
解剖学报 ›› 2017, Vol. 48 ›› Issue (1) : 19-24. DOI: 10.16098/j.issn.0529-1356.2017.01.004
神经生物学

线粒体转录终止因子蛋白家族的表达以及在MPTP / MPP+ 诱导下的表达变化

  • 张林冰 韩艳艳 仇石 许珊 左伋 刘雯*
作者信息 +

Expression and alteration induced by MPTP / MPP+of mitochondrial transcription termination factors family

  • ZHANG Lin-bing HAN Yan-yan QIU Shi XU Shan ZUO Ji LIU Wen*
Author information +
文章历史 +

摘要

目的 探讨线粒体转录终止因子(MTERFs)蛋白家族在组织和细胞中的表达以及在神经毒素MPTP/MPP+诱导下的表达变化。 方法 取正常C57BL小黑鼠的脑、肝、肾组织,以及人神经母细胞瘤细胞SH-SY5Y、人心肌细胞HCM、人肝细胞L-02,检测MTERFs的蛋白表达情况;通过MPTP/MPP+构建帕金森病(PD)动物/细胞模型,检测MTERFs的蛋白表达变化情况。 结果 MTERFs在小鼠脑中和SH-SY5Y细胞中蛋白表达水平较高;MPTP/MPP+ 诱导的PD模型中,MTERF3蛋白表达水平明显降低。 结论 在小鼠脑和SH-SY5Y细胞中,MTERFs表达较高;MPTP/MPP+诱导下MTERF3蛋白表达明显降低,影响了线粒体转录水平,这可能参与了帕金森病发生的过程。

Abstract

Objective To investigate the expression of mitochondrial transcription termination factors (MTERFs) in various tissues and cells, and the changes of MTERFs induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/1-methyl-4-pheny lpyridine(MPP+ ). Methods Western blotting was used to measure the expression of the MTERFs in brain, liver, kidney of C57BL mice and in human SH-SY5Y, HCM, L-02 cells. MPTP/MPP+ was injected to imitate PD animal/cell models. The changes of MTERFs protein were detected through western blotting. Results The expression of MTERFs was higher in mice brain and SH-SY5Y cells. In PD mouse model induced by MPTP, MTERF3 reduced significantly. Conclusion The expression of MTERFs was higher in mouse brain and SH-SY5Y cells. After induced by MPTP/MPP+ , MTERF3 decreased obviously, which increased transcription level and might involve in a process of Parkinson's disease.

关键词

线粒体转录终止因子 / 1-甲基-4-苯基-1 / 2 / 3 / 6-四氢吡啶/1-甲基-4-苯基吡啶 / 帕金森病 / 免疫印迹法 / 小鼠

Key words

Mitochondrial transcription termination factor / 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridine /   / Parkinson’s disease / Western blotting / Mouse

引用本文

导出引用
张林冰 韩艳艳 仇石 许珊 左伋 刘雯. 线粒体转录终止因子蛋白家族的表达以及在MPTP / MPP+ 诱导下的表达变化[J]. 解剖学报. 2017, 48(1): 19-24 https://doi.org/10.16098/j.issn.0529-1356.2017.01.004
ZHANG Lin-bing HAN Yan-yan QIU Shi XU Shan ZUO Ji LIU Wen. Expression and alteration induced by MPTP / MPP+of mitochondrial transcription termination factors family[J]. Acta Anatomica Sinica. 2017, 48(1): 19-24 https://doi.org/10.16098/j.issn.0529-1356.2017.01.004

参考文献

[1]Martin M, Cho J, Cesare AJ, et al. Termination factor-mediated DNA loop between termination and initiation sites drives mitochondrial rRNA synthesis[J].Cell,2005, 123 (7):1227-1240.
[2]Hyvarinen AK, Kumanto MK, Marjavaara SK, et al. Effects on mitochondrial transcription of manipulating mTERF protein levels in cultured human HEK293 cells[J]. BMC Mol Biol, 2010,11:72.
[3]Huang W, Yu M, Jiao Y, et al. Mitochondrial transcription termination factor 2 binds to entire mitochondrial DNA and negatively regulates mitochondrial gene expression[J].Acta Biochim Biophys Sin (Shanghai), 2011,43(6):472-479.
[4]Wredenberg A, Lagouge M, Bratic A, et al. MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals[J]. PLoS Genet, 2013,9(1):e1003178.
[5]Metodiev MD, Spahr H, Loguercio Polosa P, et al. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly[J]. PLoS Genet, 2014,10(2):e1004110.
[6]Ye X, Han Y, Zhang L,et al. MTERF4 regulates the mitochondrial dysfunction induced by MPP(+) in SH-SY5Y cells[J]. Biochem Biophys Res Commun, 2015,464(1):214-220.
[7]Han Y, Gao P, Qiu S, et al. MTERF2 contributes to MPP+ -induced mitochondrial dysfunction and cell damage [J].Biochem Biophys Res Commun, 2016,471(1):177-183.
[8]Reinhardt P, Schmid B, Burbulla LF, et al.Genetic correction of a LRRK2 mutation in human iPSCs linksparkinsonian neurodegeneration to ERK-dependent changes in gene expression[J].Cell Stem Cell,2013,12(3):354-367.
[9]Sohn EJ, Shin MJ, Kim DW, et al. Tat-fused recombinant human SAG prevents dopaminergic neurodegeneration in a MPTP-induced Parkinson’s disease model[J].Mol Cells, 2014,37(3):226-233.
[10]Hwang DS, Kim HG, Jang JB, et al. Dangguijakyak-san protects against 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced neuronal damage via anti-inflammatory action[J].Evid Based Complement Alternat Med, 2013,2013:976270.
[11]Roberti M, Polosa PL, Bruni F, et al. The MTERF family proteins: mitochondrial transcription regulators and beyond[J]. Biochim Biophys Acta, 2009,1787(5):303-311.
[12]Guja KE, Garcia-Diaz M. Hitting the brakes: termination of mitochondrial transcription[J]. Biochim Biophys Acta, 2012,1819(9-10):939-947.
[13]Fernandez-Silva P, Martinez-Azorin F, Micol V, et al. The human mitochondrial transcription termination factor (mTERF) is a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions[J]. EMBO J, 1997,16 (5):1066-1079.
[14]Kruse B, Narasimhan N, Attardi G. Termination of transcription in human mitochondria: identifi-cation and purification of a DNA binding protein factor that promotes termination [J]. Cell, 1989, 58(2) : 391-397.
[15]Park CB, Asin-Cayuela J, Camara Y, et al. MTERF3 is a negative regulator of mammalian mtDNA transcription[J]. Cell, 2007, 130(2):273-285.
[16]Spahr H, Samuelsson T, Hallberg BM, et al. Structure of mitochondrial transcriptiontermination factor 3 reveals a novel nucleic acid-binding domain[J]. Biochem Biophys Res Commun,2010,397(3):386-390.
[17]Camara Y, Asin-Cayuela J, Park CB, et al. MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrialribosome[J]. Cell Metab, 2011,13(5):527-539.
[18]Yakubovskaya E, Guja KE, Mejia E, et al. Structure of the essential MTERF4 : NSUN4 protein complex reveals how an MTERF protein collaborates to facilitate rRNA modification[J]. Structure,2012,20(11):1940-1947.
[19]Terzioglu M, Ruzzenente B, Harmel J, et al. MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation[J]. Cell Metab, 2013, 17(4):618-626.

基金

上海市科委基础研究重大重点项目


PDF(627 KB)

Accesses

Citation

Detail

段落导航
相关文章

/