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表达淀粉样蛋白的转基因秀丽隐杆线虫中银纳米粒子的毒性增强。

Enhanced toxicity of silver nanoparticles in transgenic Caenorhabditis elegans expressing amyloidogenic proteins.

机构信息

a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .

b Laboratory of Experimental and Clinical Toxicology, Toxicology Division, Department of Environmental Medicine , IRCCS Salvatore Maugeri Foundation, Scientific Institute of Pavia Medical Centre , Pavia , Italy .

出版信息

Amyloid. 2015;22(4):221-8. doi: 10.3109/13506129.2015.1077216. Epub 2015 Oct 14.

DOI:10.3109/13506129.2015.1077216
PMID:26466638
Abstract

The increasing number of applications of silver nanoparticles (AgNP) prompted us to assess their toxicity in vivo. We have investigated their effects on wild type and transgenic Caenorhabditis elegans (C. elegans) strains expressing two prototypic amyloidogenic proteins: β2-microglobulin and Aβ peptide3-42. The use of C. elegans allowed us to highlight AgNP toxicity in the early phase of the worm's life cycle (LC50 survival, 0.9 µg/ml). A comparative analysis of LC50 values revealed that our nematode strains were more sensitive to assess AgNP toxicity than the cell lines, classically used in toxicity tests. Movement and superoxide production in the adult population were significantly affected by exposure to AgNP; the transgenic strains were more affected than the wild type worms. Our screening approach could be applied to other types of nanomaterials that can enter the body and express any nanostructure-related bioactivities. We propose that C. elegans reproducing the molecular events associated with protein misfolding diseases, e.g. Alzheimer's disease and systemic amyloidosis, may help to investigate the specific toxicity of a range of potentially harmful molecules. Our study suggests that transgenic C. elegans may be used to predict the effect of chemicals in a "fragile population", where an underlying pathologic state may amplify their toxicity.

摘要

银纳米粒子(AgNP)的应用越来越多,促使我们评估其体内毒性。我们研究了它们对表达两种典型淀粉样蛋白的野生型和转基因秀丽隐杆线虫(C. elegans)菌株的影响:β2-微球蛋白和 Aβ肽 3-42。使用 C. elegans 使我们能够在蠕虫生命周期的早期阶段突出 AgNP 毒性(生存的 LC50,0.9μg/ml)。LC50 值的比较分析表明,与经典用于毒性测试的细胞系相比,我们的线虫菌株对评估 AgNP 毒性更为敏感。暴露于 AgNP 后,成年群体的运动和超氧化物产生显著受到影响;转基因菌株比野生型蠕虫更受影响。我们的筛选方法可应用于其他类型的纳米材料,这些纳米材料可以进入体内并表达任何与纳米结构相关的生物活性。我们提出,重现与蛋白质错误折叠疾病(例如阿尔茨海默病和系统性淀粉样变性)相关的分子事件的 C. elegans 可能有助于研究一系列潜在有害分子的特定毒性。我们的研究表明,转基因 C. elegans 可用于预测化学物质在“脆弱群体”中的作用,其中潜在的病理状态可能会放大其毒性。

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