Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles
We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 10<sup>5</sup> NPs/m<sup>3</sup>) for periods of 3 days, 2 weeks, 6 weeks, and 3 months. A whole genome tran...
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Format: | Article |
Language: | English |
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MDPI AG
2020-03-01
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Series: | Nanomaterials |
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Online Access: | https://www.mdpi.com/2079-4991/10/3/550 |
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doaj-5015e0380d1744b5aff9908fe18135fb |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pavel Rossner Kristyna Vrbova Andrea Rossnerova Tana Zavodna Alena Milcova Jiri Klema Zbynek Vecera Pavel Mikuska Pavel Coufalik Lukas Capka Kamil Krumal Bohumil Docekal Vladimir Holan Miroslav Machala Jan Topinka |
spellingShingle |
Pavel Rossner Kristyna Vrbova Andrea Rossnerova Tana Zavodna Alena Milcova Jiri Klema Zbynek Vecera Pavel Mikuska Pavel Coufalik Lukas Capka Kamil Krumal Bohumil Docekal Vladimir Holan Miroslav Machala Jan Topinka Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles Nanomaterials copper(ii) oxide nanoparticles inhalation mouse gene expression dna methylation |
author_facet |
Pavel Rossner Kristyna Vrbova Andrea Rossnerova Tana Zavodna Alena Milcova Jiri Klema Zbynek Vecera Pavel Mikuska Pavel Coufalik Lukas Capka Kamil Krumal Bohumil Docekal Vladimir Holan Miroslav Machala Jan Topinka |
author_sort |
Pavel Rossner |
title |
Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles |
title_short |
Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles |
title_full |
Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles |
title_fullStr |
Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles |
title_full_unstemmed |
Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles |
title_sort |
gene expression and epigenetic changes in mice following inhalation of copper(ii) oxide nanoparticles |
publisher |
MDPI AG |
series |
Nanomaterials |
issn |
2079-4991 |
publishDate |
2020-03-01 |
description |
We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 10<sup>5</sup> NPs/m<sup>3</sup>) for periods of 3 days, 2 weeks, 6 weeks, and 3 months. A whole genome transcriptome and miRNA analysis was performed using next generation sequencing. Global DNA methylation was assessed by ELISA. The inhalation resulted in the deregulation of mRNA transcripts: we detected 170, 590, 534, and 1551 differentially expressed transcripts after 3 days, 2 weeks, 6 weeks, and 3 months of inhalation, respectively. Biological processes and pathways affected by inhalation, differed between 3 days exposure (collagen formation) and longer treatments (immune response). Periods of two weeks exposure further induced apoptotic processes, 6 weeks of inhalation affected the cell cycle, and 3 months of treatment impacted the processes related to cell adhesion. The expression of miRNA was not affected by 3 days of inhalation. Prolonged exposure periods modified miRNA levels, although the numbers were relatively low (17, 18, and 38 miRNAs, for periods of 2 weeks, 6 weeks, and 3 months, respectively). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis based on miRNA−mRNA interactions, revealed the deregulation of processes implicated in the immune response and carcinogenesis. Global DNA methylation was not significantly affected in any of the exposure periods. In summary, the inhalation of CuO NPs impacted on both mRNA and miRNA expression. A significant transcriptomic response was already observed after 3 days of exposure. The affected biological processes and pathways indicated the negative impacts on the immune system and potential role in carcinogenesis. |
topic |
copper(ii) oxide nanoparticles inhalation mouse gene expression dna methylation |
url |
https://www.mdpi.com/2079-4991/10/3/550 |
work_keys_str_mv |
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doaj-5015e0380d1744b5aff9908fe18135fb2020-11-25T03:29:28ZengMDPI AGNanomaterials2079-49912020-03-0110355010.3390/nano10030550nano10030550Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide NanoparticlesPavel Rossner0Kristyna Vrbova1Andrea Rossnerova2Tana Zavodna3Alena Milcova4Jiri Klema5Zbynek Vecera6Pavel Mikuska7Pavel Coufalik8Lukas Capka9Kamil Krumal10Bohumil Docekal11Vladimir Holan12Miroslav Machala13Jan Topinka14Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Computer Science, Czech Technical University in Prague, 12135 Prague, Czech RepublicDepartment of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech RepublicDepartment of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech RepublicDepartment of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech RepublicDepartment of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech RepublicDepartment of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech RepublicDepartment of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech RepublicDepartment of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Chemistry and Toxicology, Veterinary Research Institute, 62100 Brno, Czech RepublicDepartment of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech RepublicWe investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 10<sup>5</sup> NPs/m<sup>3</sup>) for periods of 3 days, 2 weeks, 6 weeks, and 3 months. A whole genome transcriptome and miRNA analysis was performed using next generation sequencing. Global DNA methylation was assessed by ELISA. The inhalation resulted in the deregulation of mRNA transcripts: we detected 170, 590, 534, and 1551 differentially expressed transcripts after 3 days, 2 weeks, 6 weeks, and 3 months of inhalation, respectively. Biological processes and pathways affected by inhalation, differed between 3 days exposure (collagen formation) and longer treatments (immune response). Periods of two weeks exposure further induced apoptotic processes, 6 weeks of inhalation affected the cell cycle, and 3 months of treatment impacted the processes related to cell adhesion. The expression of miRNA was not affected by 3 days of inhalation. Prolonged exposure periods modified miRNA levels, although the numbers were relatively low (17, 18, and 38 miRNAs, for periods of 2 weeks, 6 weeks, and 3 months, respectively). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis based on miRNA−mRNA interactions, revealed the deregulation of processes implicated in the immune response and carcinogenesis. Global DNA methylation was not significantly affected in any of the exposure periods. In summary, the inhalation of CuO NPs impacted on both mRNA and miRNA expression. A significant transcriptomic response was already observed after 3 days of exposure. The affected biological processes and pathways indicated the negative impacts on the immune system and potential role in carcinogenesis.https://www.mdpi.com/2079-4991/10/3/550copper(ii) oxide nanoparticlesinhalationmousegene expressiondna methylation |