Nrf2 alleviates radiation-induced rectal injury by inhibiting of necroptosis.
Biochem Biophys Res Commun
; 554: 49-55, 2021 05 21.
Article
en En
| MEDLINE
| ID: mdl-33774279
ABSTRACT
Radiation-induced rectal injury is one of the common side effects of pelvic radiation therapy. This study aimed to explore the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in this process. In vivo, knockout (KO) of Nrf2 led to aggravated radiation-induced histological changes in the rectums. In vitro, interference or overexpression of Nrf2 resulted in enhanced or reduced radiosensitivity in human intestinal epithelial crypts (HIEC) cells, respectively. A potential relationship between Nrf2 and necroptosis was identified using RNA sequencing (RNA-seq) and western blotting (WB), which showed that necroptosis-related proteins were negatively correlated with Nrf2. Upon treatment with necrostatin-1 (Nec-1), the increased radiosensitivity, decreased cell viability, increased γH2AX foci formation, and decreased mitochondrial membrane potential (MMP) in Nrf2-interfered HIEC cells were alleviated. A significant recovery in morphological alterations was also observed in Nrf2 KO mice administered with Nec-1. Taken together, our results highlight the important protective effect of Nrf2 in radiation-induced rectal injury through the inhibition of necroptosis, and the physiological significance of necroptosis in radiation-induced rectal injury.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Traumatismos por Radiación
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Recto
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Factor 2 Relacionado con NF-E2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
China