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ID 67720
フルテキストURL
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著者
Tsuchida, Tomoki Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kubota, Sho Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kamiuezono, Shizuki Department of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University
Takasugi, Nobumasa Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ito, Akihiro School of Life Sciences, Tokyo University of Pharmacy and Life Sciences
Kumagai, Yoshito Graduate School of Pharmaceutical Sciences, Kyushu University
Uehara, Takashi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID Kaken ID
抄録
Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses. A total of 45 environmental electrophiles were screened for inhibitory effects on the activity of DNA methyltransferase 3B (DNMT3B), a key enzyme in DNA methylation, and four compounds were identified. We focused on 1,2-naphthoquinone (1,2-NQ), an air pollutant whose toxicity has been reported previously. Interestingly, we found that 1,2-NQ modified multiple lysine and histidine residues in DNMT3B, one of which was near the active site in DNMT3B. It was found that 1,2-NQ altered gene expression and evoked inflammatory responses in lung adenocarcinoma cell lines. Furthermore, we found that 1,2-NQ upregulated CXCL8 expression through DNA demethylation of the distal enhancer and promoted cancer cell growth. Our study reveals novel mechanisms of epigenetic regulation by environmental electrophiles through the inhibition of DNMT3B activity and suggests their physiological impact.
キーワード
DNA methylation
DNA methyltransferase
chemical modification
chemokine
cell proliferation
toxicology
exposome
environmental electrophiles
発行日
2024-10-29
出版物タイトル
International Journal of Molecular Sciences
25巻
21号
出版者
MDPI
開始ページ
11592
ISSN
1661-6596
資料タイプ
学術雑誌論文
言語
英語
OAI-PMH Set
岡山大学
著作権者
© 2024 by the authors.
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.3390/ijms252111592
ライセンス
https://creativecommons.org/licenses/by/4.0/
Citation
Tsuchida, T.; Kubota, S.; Kamiuezono, S.; Takasugi, N.; Ito, A.; Kumagai, Y.; Uehara, T. Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition. Int. J. Mol. Sci. 2024, 25, 11592. https://doi.org/10.3390/ijms252111592
助成機関名
Ministry of Education, Culture, Sports, Science and Technology
Smoking Research Foundation
Japan Science and Technology Agency
助成番号
22K19380
24H00678
24K09795
JPMJSP2126
JPMJFS2128