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Subtoxic dose of lithium cobalt oxide nanosheets impacts critical molecular pathways in trout gill epithelial cells
Environmental Science: Nano ( IF 5.8 ) Pub Date : 2020-10-20 , DOI: 10.1039/d0en00844c
Arielle C. Mensch 1, 2, 3, 4 , Hugh D. Mitchell 2, 3, 4, 5 , Lye Meng Markillie 1, 2, 3, 4 , Elizabeth D. Laudadio 4, 6, 7, 8 , Jenny K. Hedlund Orbeck 4, 6, 7, 8 , Alice Dohnalkova 1, 2, 3, 4 , Michael P. Schwartz 4, 6, 7, 8 , Robert J. Hamers 4, 6, 7, 8 , Galya Orr 1, 2, 3, 4
Affiliation  

Increasing use of nanoscale lithium cobalt oxide (LCO) particles in nanotechnologies, including catalysis and energy storage, raises concerns over their release into the environment and subsequent biological impact. Here we study the impact of LCO nanosheets on trout gill epithelial cells – model cells for environmental exposures – by global transcriptomics using RNA-Seq. We identify molecular processes impacted by subtoxic and toxic nanoparticle (NP) doses as well as dissolved Li+ and Co2+ ions. We found that the ions, at concentrations released from the toxic NP dose, did not impact cell viability and downregulated the expression of few genes following 24 h exposure, which recovered to normal levels at 48 h. In contrast, the toxic NP dose upregulated the expression of over 1000 genes at each time point, indicating the intact NPs are responsible for perturbing gene expression and toxicity. Importantly, the subtoxic NP dose, despite having no impact on cell viability, upregulated the expression of over 500 genes at 24 h, and 150 genes at 48 h. Clustering analysis showed distinct gene expression profiles induced by the toxic and subtoxic NP doses, and functional enrichment identified pathways with distinct patterns of regulations. The impacted pathways fell into four main functional categories: metabolic and energy related processes, oxygen and hypoxia related processes, membrane binding and internalization processes, and developmental processes. Together, our observations indicate that LCO NP toxicity originates from the intact NP, not the dissolved ions, and even subtoxic NP dose impacts multiple pathways critical to the normal function of the cell.

中文翻译:

亚毒性剂量的钴酸锂纳米片影响鳟鱼g上皮细胞中的关键分子途径

纳米级钴酸锂(LCO)纳米颗粒在纳米技术(包括催化和能量存储)中的使用日益增加,引起人们对其向环境中释放以及随后的生物影响的关注。在这里,我们使用RNA-Seq通过全球转录组学研究了LCO纳米片对鳟鱼g上皮细胞(环境暴露的模型细胞)的影响。我们确定了受亚毒性和有毒纳米颗粒(NP)剂量以及溶解的Li +和Co 2+影响的分子过程离子。我们发现,在有毒NP剂量释放的浓度下,离子不会影响细胞活力,并且在暴露24小时后下调了少数基因的表达,这些基因在48小时后恢复了正常水平。相反,毒性NP剂量在每个时间点上调了1000多个基因的表达,这表明完整的NP会干扰基因表达和毒性。重要的是,亚毒性NP剂量尽管对细胞生存力没有影响,但在24小时时上调了500多个基因,在48小时时上调了150个基因。聚类分析显示了有毒和亚毒性NP剂量诱导的不同基因表达谱,功能富集确定了具有不同调控模式的途径。受影响的途径分为四个主要功能类别:代谢和能量相关过程,氧气和缺氧相关过程,膜结合和内在化过程以及发育过程。总之,我们的观察结果表明,LCO NP毒性源自完整的NP,而不是溶解的离子,甚至亚毒性NP剂量也会影响对细胞正常功能至关重要的多种途径。
更新日期:2020-11-03
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