Isorhamnetin promotes 53BP1 recruitment through the enhancement of ATM phosphorylation and protects mice from radiation gastrointestinal syndrome

Yuichi Nishiyama, Akinori Morita, Shogo Tatsuta, Misaki Kanamaru, Masahiro Sakaue, Kenta Ueda, Manami Shono, Rie Fujita, Bing Wang, Yoshio Hosoi, Shin Aoki, Takeshi Sugai

Research output: Contribution to journalArticlepeer-review

Abstract

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 reg-ulator 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, iso-rhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irra-diation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair pro-cess, which is presumably associated with the suppressive effect against GI syndrome.

Original languageEnglish
Article number1514
JournalGenes
Volume12
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • 53BP1
  • ATM
  • DNA damage response
  • Isorhamnetin
  • P53
  • P53 target genes
  • PS1981-ATM
  • Radiation gastrointestinal syndrome
  • Radiation hematopoietic syndrome
  • γH2AX

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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