Highlighted Paper selected by Editor-in-Chief : Silver Nanoparticles Induce DNA Hypomethylation through Proteasome-Mediated Degradation of DNA Methyltransferase 1

  • Maki Ayaka
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University
  • Lin Ying
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University
  • Aoyama Michihiko
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University
  • Sato Kenta
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University
  • Gao Jian-Qing
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University
  • Tsujino Hirofumi
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University
  • Nagano Kazuya
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University
  • Higashisaka Kazuma
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University Department of Legal Medicine, Osaka University Graduate School of Medicine
  • Tsutsumi Yasuo
    Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University Global Center for Medical Engineering and Informatics, Osaka University

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  • Silver Nanoparticles Induce DNA Hypomethylation through Proteasome-Mediated Degradation of DNA Methyltransferase 1

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<p>Nanoparticles are used in many fields and in everyday products. Silver nanoparticles are the most frequently used nanoparticles; for example, in food-related products, owing to their antibacterial activity. However, it has been pointed out that they might have unexpected biological effects, and evaluation of their effects is underway. Although there is a growing body of evidence that nanoparticles can also induce epigenetic changes, there is still little information on the underlying mechanisms. Here, we evaluated changes in DNA methylation induced by silver nanoparticles and attempted to elucidate the induction mechanism. Immunofluorescence staining analysis revealed that silver nanoparticles with a diameter of 10, 50, or 100 nm (nAg10, nAg50, and nAg100, respectively) decreased the content of methylated DNA in A549 alveolar epithelial cells. The level of DNA methyltransferase 1 (Dnmt1) protein, which is involved in maintaining methylation during DNA replication, was significantly decreased, whereas that of Dnmt3b, which is responsible for de novo DNA methylation, was significantly increased by nAg10 treatment. Co-treatment with nAg10 and cycloheximide, which inhibits translation by inhibiting the translocation step of protein synthesis, decreased the level of Dnmt1 in comparison with nAg10-treated A549 cells, indicating a post-translational effect of nAg10. Furthermore, pretreatment with the proteasome inhibitor lactacystin restored the levels of Dnmt1 protein and DNA methylation in nAg10-treated cells. Collectively, these results suggest that nAg10 induced DNA hypomethylation through a proteasome-mediated degradation of Dnmt1.</p>

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