Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents.
Nat Commun
; 10(1): 2538, 2019 06 10.
Article
em En
| MEDLINE
| ID: mdl-31182708
ABSTRACT
The pathological mechanisms of radiation ulcer remain unsolved and there is currently no effective medicine. Here, we demonstrate that persistent DNA damage foci and cell senescence are involved in radiation ulcer development. Further more, we identify cordycepin, a natural nucleoside analogue, as a potent drug to block radiation ulcer (skin, intestine, tongue) in rats/mice by preventing cell senescence through the increase of NRF2 nuclear expression (the assay used is mainly on skin). Finally, cordycepin is also revealed to activate AMPK by binding with the α1 and γ1 subunit near the autoinhibitory domain of AMPK, then promotes p62-dependent autophagic degradation of Keap1, to induce NRF2 dissociate from Keap1 and translocate to the nucleus. Taken together, our findings identify cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, and activation of AMPK or NRF2 may thus represent therapeutic targets for preventing cell senescence and radiation ulcer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Experimentais por Radiação
/
Úlcera
/
Dano ao DNA
/
Desoxiadenosinas
/
Senescência Celular
/
Fator 2 Relacionado a NF-E2
/
Proteínas Quinases Ativadas por AMP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China