Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome.
Genes (Basel)
; 12(10)2021 09 26.
Article
em En
| MEDLINE
| ID: mdl-34680909
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 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.
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Base de dados:
MEDLINE
Assunto principal:
Quercetina
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Protetores contra Radiação
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Síndrome Aguda da Radiação
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Proteína 1 de Ligação à Proteína Supressora de Tumor p53
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Mucosa Intestinal
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article