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アイテム
Heavy water inhibits DNA double-strand break repairs and disturbs cellular transcription, presumably via quantum-level mechanisms of kinetic isotope effects on hydrolytic enzyme reactions
https://repo.qst.go.jp/records/2000664
https://repo.qst.go.jp/records/2000664ac839c88-7ba4-4715-877a-c7ec2267629e
| 名前 / ファイル | ライセンス | アクション |
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journal.pone.0309689.pdf (4.4 MB)
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| アイテムタイプ | 学術雑誌論文 / Journal Article(1) | |||||||||||||||||||||||
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| 公開日 | 2025-01-30 | |||||||||||||||||||||||
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| タイトル | Heavy water inhibits DNA double-strand break repairs and disturbs cellular transcription, presumably via quantum-level mechanisms of kinetic isotope effects on hydrolytic enzyme reactions | |||||||||||||||||||||||
| 言語 | en | |||||||||||||||||||||||
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| 言語 | eng | |||||||||||||||||||||||
| 資源タイプ | ||||||||||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||||||||
| 著者 |
Yasuda Takeshi
× Yasuda Takeshi
× Nakajima Nakako
× Tomoo Ogi
× Yanaka Tomoko
× Tanaka Izumi
× Gotoh Takaya
× Wataru Kagawa
× Kaoru Sugasawa
× Tajima Katsushi
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| 抄録 | ||||||||||||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||||||||||||
| 内容記述 | Heavy water, containing the heavy hydrogen isotope, is toxic to cells, although the underlying mechanism remains incompletely understood. In addition, certain enzymatic proton transfer reactions exhibit kinetic isotope effects attributed to hydrogen isotopes and their temperature dependencies, indicative of quantum tunneling phenomena. However, the correlation between the biological effects of heavy water and the kinetic isotope effects mediated by hydrogen isotopes remains elusive. In this study, we elucidated the kinetic isotope effects arising from hydrogen isotopes of water and their temperature dependencies in vitro, focusing on deacetylation, DNA cleavage, and protein cleavage, which are crucial enzymatic reactions mediated by hydrolysis. Intriguingly, the intracellular isotope effects of heavy water, related to the in vitro kinetic isotope effects, significantly impeded multiple DNA double-strand break repair mechanisms crucial for cell survival. Additionally, heavy water exposure enhanced histone acetylation and associated transcriptional activation in cells, consistent with the in vitro kinetic isotope effects observed in histone deacetylation reactions. Moreover, as observed for the in vitro kinetic isotope effects, the cytotoxic effect on cell proliferation induced by heavy water exhibited temperature-dependency. These findings reveal the substantial impact of heavy water-induced isotope effects on cellular functions governed by hydrolytic enzymatic reactions, potentially mediated by quantum-level mechanisms underlying kinetic isotope effects. | |||||||||||||||||||||||
| 書誌情報 |
PLOS One 巻 19, 号 10, p. e0309689, 発行日 2024-10 |
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| 識別子タイプ | DOI | |||||||||||||||||||||||
| 関連識別子 | 10.1371/journal.pone.0309689 | |||||||||||||||||||||||
