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微囊藻毒素-LR对青鳉鱼肝细胞器和膜蛋白影响的蛋白质组学研究

Proteomic study of the effects of microcystin-LR on organelle and membrane proteins in medaka fish liver.

作者信息

Malécot Mélodie, Mezhoud Karim, Marie Arul, Praseuth Danièle, Puiseux-Dao Simone, Edery Marc

机构信息

CNRS, FRE 3206 Molécules de communication et adaptation des microorganismes, and MNHN, USM 505 Cyanobactéries, cyanotoxines et environnement, Département Régulations, développement et diversité moléculaire, Muséum national d'Histoire naturelle, Paris Cedex 05, France.

出版信息

Aquat Toxicol. 2009 Aug 31;94(2):153-61. doi: 10.1016/j.aquatox.2009.06.012. Epub 2009 Jun 26.

DOI:10.1016/j.aquatox.2009.06.012
PMID:19628287
Abstract

The microcystin-leucine-arginine toxin (MC-LR) is produced by cyanobacteria that sometimes bloom in water reservoirs. It targets the liver, thus posing potential health risks to human and animals. Microcystin inhibits the protein phosphatases PP1 and PP2A, leading to diverse cellular deregulation processes. A proteomic approach was applied to the medaka fish (Oryzias latipes) to obtain an overview of the effects of MC-LR on the liver. As membrane and organelle proteins are major structural and functional components of several cell signalling pathways, we decided to investigate here the membrane and organelle-enriched fractions from the livers of control and MC-LR treated medaka fish. Seventeen proteins were identified by proteomic analysis as being modulated in response to MC-LR treatment. This is the first time for eight of them to be reported as being involved in MC-LR effects: prohibitin, fumarylacetoacetase, protein disulfide isomerase A4 and A6, glucose regulated protein 78kDa, 40S ribosomal protein SA, cytochrome b5, and ATP synthase mitochondrial d subunit. These proteins are involved in protein maturation or in the response to oxidative stress highlighting the role of organelles in protein processing and the complex cooperation associated with oxidative stress.

摘要

微囊藻毒素 - 亮氨酸 - 精氨酸毒素(MC-LR)由蓝藻产生,蓝藻有时会在水库中大量繁殖。它以肝脏为靶点,因此对人类和动物构成潜在健康风险。微囊藻毒素会抑制蛋白磷酸酶PP1和PP2A,导致多种细胞失调过程。采用蛋白质组学方法研究青鳉鱼(Oryzias latipes),以全面了解MC-LR对肝脏的影响。由于膜蛋白和细胞器蛋白是多种细胞信号通路的主要结构和功能成分,我们决定在此研究对照和MC-LR处理的青鳉鱼肝脏中富含膜和细胞器的组分。通过蛋白质组学分析鉴定出17种蛋白质在MC-LR处理后发生了调节变化。其中8种蛋白质首次被报道与MC-LR的作用有关:抗增殖蛋白、富马酰乙酰乙酸酯酶、蛋白二硫键异构酶A4和A6、葡萄糖调节蛋白78kDa、40S核糖体蛋白SA、细胞色素b5和ATP合酶线粒体d亚基。这些蛋白质参与蛋白质成熟或对氧化应激的反应,突出了细胞器在蛋白质加工中的作用以及与氧化应激相关的复杂协作。

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