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斑马鱼(Danio rerio)大脑中暴露于慢性微囊藻毒素-LR 的蛋白质图谱。

Protein profiles in zebrafish (Danio rerio) brains exposed to chronic microcystin-LR.

机构信息

State Key Laboratory of Marine Environmental Science/Environmental Science Research Center, Xiamen University, Xiamen 361005, People's Republic of China.

出版信息

Chemosphere. 2010 Oct;81(6):716-24. doi: 10.1016/j.chemosphere.2010.07.061. Epub 2010 Aug 25.

Abstract

Microcystin-LR (MCLR) is a commonly encountered blue-green algal hepatotoxin and a known inhibitor of cellular protein phosphatase (PP), however, little is known about its neurotoxicity. This study investigated the protein profiles of zebrafish (Danio rerio) brains chronically exposed to MCLR concentrations (2 or 20 μg L(-1)) using the proteomic approach. The results showed that MCLR strikingly enhanced toxin accumulation and the PP activity in zebrafish brains after 30 d exposure. Comparison of two-dimensional electrophoresis protein profiles of MCLR exposed and non-exposed zebrafish brains revealed that the abundance of 30 protein spots was remarkably altered in response to MCLR exposure. These proteins are involved in cytoskeleton assembly, macromolecule metabolism, oxidative stress, signal transduction, and other functions (e.g. transporting, protein degradation, apoptosis and translation), indicating that MCLR toxicity in the fish brain is complex and diverse. The chronic neurotoxicity of MCLR might initiate the PP pathway via an upregulation of PP2C in the zebrafish brain, in addition to the reactive oxygen species pathway. Additionally, the increase of vitellogenin abundance in MCLR exposed zebrafish brains suggested that MCLR might mimic the effects of endocrine disrupting chemicals. This study demonstrated that MCLR causes neurotoxicity in zebrafish at the proteomic level, which provides a new insight into MCLR toxicity in aquatic organisms and human beings.

摘要

微囊藻毒素-LR(MCLR)是一种常见的蓝绿藻肝毒素,也是细胞蛋白磷酸酶(PP)的已知抑制剂,但其神经毒性知之甚少。本研究采用蛋白质组学方法研究了斑马鱼(Danio rerio)大脑在慢性暴露于 MCLR 浓度(2 或 20 μg L(-1)) 下的蛋白质谱。结果表明,MCLR 在 30d 暴露后显著增强了斑马鱼大脑中的毒素积累和 PP 活性。比较暴露和未暴露于 MCLR 的斑马鱼大脑的二维电泳蛋白质谱发现,30 个蛋白质斑点的丰度因 MCLR 暴露而明显改变。这些蛋白质参与细胞骨架组装、大分子代谢、氧化应激、信号转导和其他功能(例如转运、蛋白质降解、细胞凋亡和翻译),表明 MCLR 对鱼脑的毒性是复杂多样的。慢性 MCLR 神经毒性可能通过在斑马鱼脑中上调 PP2C 来启动 PP 途径,除了活性氧途径。此外,暴露于 MCLR 的斑马鱼大脑中卵黄蛋白原丰度的增加表明 MCLR 可能模拟内分泌干扰化学物质的作用。本研究表明 MCLR 在蛋白质组水平上对斑马鱼造成神经毒性,为 MCLR 在水生生物和人类中的毒性提供了新的见解。

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