期刊
GENES
卷 12, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/genes12101514
关键词
isorhamnetin; radiation hematopoietic syndrome; radiation gastrointestinal syndrome; DNA damage response; p53; p53 target genes; 53BP1; ATM; pS1981-ATM; gamma H2AX
资金
- KAKENHI from the Japan Society for the Promotion of Science [19H03604, 21K07644]
Isorhamnetin has been found to possess radioprotective effects by enhancing the ATM-dependent DNA repair process, which may be associated with its suppressive effect against gastrointestinal syndrome.
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, isorhamnetintreated 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.
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