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甲基汞、阿散酸和达氟沙星对小鼠胚胎干细胞向神经细胞分化的毒性作用。

Toxic effects of methylmercury, arsanilic acid and danofloxacin on the differentiation of mouse embryonic stem cells into neural cells.

作者信息

Kang Seok-Jin, Jeong Sang-Hee, Kim Eun-Joo, Park Young-Il, Park Sung-Won, Shin Hyo-Sook, Son Seong-Wan, Kang Hwan-Goo

机构信息

Toxicology and Residue Chemistry Division, Animal and Plant Quarantine Agency, Anyang 430-824, Korea.

出版信息

J Vet Sci. 2014;15(1):61-71. doi: 10.4142/jvs.2014.15.1.61. Epub 2013 Oct 18.

Abstract

This study was performed to assess the neurotoxic effects of methylmercury, arsanilic acid and danofloxacin by quantification of neural-specific proteins in vitro. Quantitation of the protein markers during 14 days of differentiation indicated that the mouse ESCs were completely differentiated into neural cells by Day 8. The cells were treated with non-cytotoxic concentrations of three chemicals during differentiation. Low levels of exposure to methylmercury decreased the expression of GABAA-R and Nestin during the differentiating stage, and Nestin during the differentiated stage. In contrast, GFAP, Tuj1, and MAP2 expression was affected only by relatively high doses during both stages. Arsanilic acid affected the levels of GABAA-R and GFAP during the differentiated stage while the changes of Nestin and Tuj1 were greater during the differentiating stage. For the neural markers (except Nestin) expressed during both stages, danofloxacin affected protein levels at lower concentrations in the differentiated stage than the differentiating stage. Acetylcholinesterase activity was inhibited by relatively low concentrations of methylmercury and arsanilic acid during the differentiating stage while this activity was inhibited only by more than 40 μM of danofloxacin in the differentiated stage. Our results provide useful information about the different toxicities of chemicals and the impact on neural development.

摘要

本研究旨在通过体外定量神经特异性蛋白来评估甲基汞、对氨基苯胂酸和达氟沙星的神经毒性作用。在分化的14天内对蛋白质标志物进行定量分析表明,到第8天小鼠胚胎干细胞已完全分化为神经细胞。在分化过程中,用三种化学物质的无细胞毒性浓度处理细胞。低水平接触甲基汞会降低分化阶段的GABAA-R和巢蛋白表达,以及分化后阶段的巢蛋白表达。相比之下,胶质纤维酸性蛋白(GFAP)、βIII微管蛋白(Tuj1)和微管相关蛋白2(MAP2)的表达仅在两个阶段受到相对高剂量的影响。对氨基苯胂酸在分化后阶段影响GABAA-R和GFAP的水平,而巢蛋白和Tuj1在分化阶段的变化更大。对于在两个阶段都表达的神经标志物(巢蛋白除外),达氟沙星在分化后阶段比分化阶段以更低浓度影响蛋白水平。在分化阶段,相对低浓度的甲基汞和对氨基苯胂酸可抑制乙酰胆碱酯酶活性,而在分化后阶段,仅超过40μM的达氟沙星才能抑制该活性。我们的结果提供了有关化学物质不同毒性及其对神经发育影响的有用信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3860/3973767/dc68b32027e1/jvs-15-61-g001.jpg

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