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模式生物秀丽隐杆线虫暴露于金纳米颗粒的毒代基因组学反应。

Toxicogenomic responses of the model organism Caenorhabditis elegans to gold nanoparticles.

机构信息

Department of Plant and Soil Sciences, University of Kentucky, Lexington, Kentucky 40546, United States.

出版信息

Environ Sci Technol. 2012 Apr 3;46(7):4115-24. doi: 10.1021/es2033108. Epub 2012 Mar 13.

DOI:10.1021/es2033108
PMID:22372763
Abstract

We used Au nanoparticles (Au-NPs) as a model for studying particle-specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, Caenorhabditis elegans . Global genome expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC(10) level (5.9 mg·L(-1)) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways associated with 38 of these genes were identified. Up-regulation of 26 pqn/abu genes from noncanonical unfolded protein response (UPR) pathway and molecular chaperones (hsp-16.1, hsp-70, hsp-3, and hsp-4) were observed and are likely indicative of endoplasmic reticulum stress. Significant increase in sensitivity to Au-NPs in a mutant from noncanonical UPR (pqn-5) suggests possible involvement of the genes from this pathway in a protective mechanism against Au-NPs. Significant responses to Au-NPs in endocytosis mutants (chc-1 and rme-2) provide evidence for endocytosis pathway being induced by Au-NPs. These results demonstrate that Au-NPs are bioavailable and cause adverse effects to C. elegans by activating both general and specific biological pathways. The experiments with mutants further support involvement of several of these pathways in Au-NP toxicity and/or detoxification.

摘要

我们使用金纳米颗粒(Au-NPs)作为模型,通过研究模式土壤生物秀丽隐杆线虫中的毒代基因组反应,来研究制造纳米材料(MNMs)的颗粒特异性效应。在暴露于 LC(10)水平(5.9 mg·L(-1))的 4nm 柠檬酸盐包覆的 Au-NPs 下,线虫的全基因组表达显示 797 个基因的表达有显著差异。使用 qRT-PCR 独立验证了五个基因(apl-1、dyn-1、act-5、abu-11 和 hsp-4)的表达水平。确定了与其中 38 个基因相关的七个常见生物学途径。非经典未折叠蛋白反应(UPR)途径和分子伴侣(hsp-16.1、hsp-70、hsp-3 和 hsp-4)中的 26 个 pqn/abu 基因上调,这可能表明内质网应激。非经典 UPR(pqn-5)突变体对 Au-NPs 的敏感性显著增加,这表明该途径的基因可能参与了针对 Au-NPs 的保护机制。内吞作用突变体(chc-1 和 rme-2)对 Au-NPs 的显著反应为 Au-NPs 诱导内吞作用途径提供了证据。这些结果表明,Au-NPs 是生物可利用的,并通过激活一般和特定的生物学途径对秀丽隐杆线虫造成不利影响。与突变体的实验进一步支持这些途径中的几个参与 Au-NP 毒性和/或解毒。

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