Šíma Michal , Líbalová Helena , Závodná Táňa , Vrbová Kristýna , Kléma Jiří , Rössner Pavel
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引用次数: 0
摘要
我们分析了暴露于金属基纳米材料(NMs)[TiO2(NM-100)、ZnO(NM-110)、SiO2(NM-200)、Ag(NM-300 K)]的 THP-1 细胞的基因表达。对显著差异表达基因(DEGs)的功能富集分析确定了关键的调节生物过程和途径。DEGs 被用于构建蛋白质-蛋白质相互作用网络。NM-110 和 NM-300 K 诱导了涉及氧化和基因毒性应激、免疫反应、细胞周期改变、金属离子解毒和氧化还原敏感通路调控的基因表达变化。两种 NMs 都共享一些高度连接的蛋白质节点(枢纽),包括 CXCL8、ATF3、HMOX1 和 IL1B。NM-200 诱导了有限的转录变化,其中大部分与免疫反应有关;然而,几个枢纽(CXCL8、ATF3)与 NM-110 和 NM-300 K 相同。没有观察到 NM-100 的影响。总之,可溶性纳米材料 NM-110 和 NM-300 K 产生了多种毒性效应,而不溶性纳米材料 NM-200 引发了免疫毒性;NM-100 在基因表达水平上没有引起可检测到的变化。
Gene expression profiles and protein-protein interaction networks in THP-1 cells exposed to metal-based nanomaterials
We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO2 (NM-100), ZnO (NM-110), SiO2 (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein–protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.
期刊介绍:
Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man.
Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals.
In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.