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Article

Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome

1
Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
2
Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan
3
National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
4
Department of Radiation Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan
5
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Junya Kobayashi
Genes 2021, 12(10), 1514; https://doi.org/10.3390/genes12101514
Received: 31 August 2021 / Revised: 22 September 2021 / Accepted: 24 September 2021 / Published: 26 September 2021
Flavonoids are a subclass of polyphenols which are attractive, due to possessing various physiological activities, including a radioprotective effect. Tumor suppressor p53 is a primary regulator in the radiation response and is involved in the pathogenesis of radiation injuries. In this study, we revealed that isorhamnetin inhibited radiation cell death, and investigated its action mechanism focusing on DNA damage response. Although isorhamnetin moderated p53 activity, it promoted phosphorylation of ataxia telangiectasia mutated (ATM) and enhanced 53BP1 recruitment in irradiated cells. The radioprotective effect of isorhamnetin was not observed in the presence of ATM inhibitor, indicating that its protective effect was dependent on ATM. Furthermore, isorhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irradiation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair process, which is presumably associated with the suppressive effect against GI syndrome. View Full-Text
Keywords: isorhamnetin; radiation hematopoietic syndrome; radiation gastrointestinal syndrome; DNA damage response; p53; p53 target genes; 53BP1; ATM; pS1981-ATM; γH2AX isorhamnetin; radiation hematopoietic syndrome; radiation gastrointestinal syndrome; DNA damage response; p53; p53 target genes; 53BP1; ATM; pS1981-ATM; γH2AX
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MDPI and ACS Style

Nishiyama, Y.; Morita, A.; Tatsuta, S.; Kanamaru, M.; Sakaue, M.; Ueda, K.; Shono, M.; Fujita, R.; Wang, B.; Hosoi, Y.; Aoki, S.; Sugai, T. Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome. Genes 2021, 12, 1514. https://doi.org/10.3390/genes12101514

AMA Style

Nishiyama Y, Morita A, Tatsuta S, Kanamaru M, Sakaue M, Ueda K, Shono M, Fujita R, Wang B, Hosoi Y, Aoki S, Sugai T. Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome. Genes. 2021; 12(10):1514. https://doi.org/10.3390/genes12101514

Chicago/Turabian Style

Nishiyama, Yuichi, Akinori Morita, Shogo Tatsuta, Misaki Kanamaru, Masahiro Sakaue, Kenta Ueda, Manami Shono, Rie Fujita, Bing Wang, Yoshio Hosoi, Shin Aoki, and Takeshi Sugai. 2021. "Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome" Genes 12, no. 10: 1514. https://doi.org/10.3390/genes12101514

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