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工业相关硅锰尘对人 1321N1 星形胶质细胞瘤细胞毒性的作用机制:一项体外研究。

Mechanisms of Toxicity of Industrially Relevant Silicomanganese Dust on Human 1321N1 Astrocytoma Cells: An In Vitro Study.

机构信息

Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Pb 8149 Dep., N-0033 Oslo, Norway.

Department of Industrial Process, Technology SINTEF Materials and Chemistry, PB 4760, N-7465 Trondheim, Norway.

出版信息

Int J Mol Sci. 2019 Feb 10;20(3):740. doi: 10.3390/ijms20030740.

DOI:10.3390/ijms20030740
PMID:30744184
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6386893/
Abstract

Tremendous efforts are applied in the ferroalloy industry to control and reduce exposure to dust generated during the production process, as inhalable Mn-containing particulate matter has been linked to neurodegenerative diseases. This study aimed to investigate the toxicity and biological effects of dust particles from laboratory-scale processes where molten silicomanganese (SiMn) was exposed to air, using a human astrocytoma cell line, 1321N1, as model system. Characterization of the dust indicated presence of both nano-sized and larger particles averaging between 100 and 300 nm. The dust consisted mainly of Si, Mn and O. Investigation of cellular mechanisms showed a dose- and time-dependent effect on cell viability, with only minor changes in the expression of proteins involved in apoptosis. Moreover, gene expression of the neurotoxic biomarker () increased, whereas APP protein expression decreased. Finally, induction of gap junctional intercellular communication (GJIC) increased with higher doses and correlated with the other endpoints. Thus, the effects of SiMn dust on 1321N1 cells are highly dependent on the dose of exposure and involves changes in APP, apoptosis-related proteins and intercellular communication.

摘要

在铁合金行业,人们付出了巨大努力来控制和减少生产过程中产生的粉尘暴露,因为可吸入的含锰颗粒物与神经退行性疾病有关。本研究旨在利用人星形胶质细胞瘤细胞系 1321N1 作为模型系统,研究在实验室规模下熔融硅锰(SiMn)暴露于空气中时产生的粉尘颗粒的毒性和生物学效应。对粉尘的特性分析表明,其存在纳米级和较大粒径的颗粒,平均粒径在 100 至 300nm 之间。该粉尘主要由 Si、Mn 和 O 组成。细胞机制的研究表明,细胞活力具有剂量和时间依赖性效应,而参与细胞凋亡的蛋白表达仅有轻微变化。此外,神经毒性生物标志物()的基因表达增加,而 APP 蛋白表达减少。最后,随着剂量的增加,缝隙连接细胞间通讯(GJIC)的诱导增加,并且与其他终点相关。因此,SiMn 粉尘对 1321N1 细胞的影响高度依赖于暴露剂量,并涉及 APP、凋亡相关蛋白和细胞间通讯的变化。

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本文引用的文献

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Int J Mol Sci. 2019 Jan 16;20(2):358. doi: 10.3390/ijms20020358.
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Connexin 43 Controls the Astrocyte Immunoregulatory Phenotype.连接蛋白43控制星形胶质细胞的免疫调节表型。
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The role of astrocytes in amyloid production and Alzheimer's disease.星形胶质细胞在淀粉样蛋白生成和阿尔茨海默病中的作用。
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The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines.二氧化硅纳米颗粒对胶质母细胞瘤细胞系凋亡和自噬的影响
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