Nrf2 inhibition affects cell cycle progression during early mouse embryo development.
J Reprod Dev
; 64(1): 49-55, 2018 Feb 27.
Article
em En
| MEDLINE
| ID: mdl-29249781
ABSTRACT
Brusatol, a quassinoid isolated from the fruit of Bruceajavanica, has recently been shown to inhibit nuclear factor erythroid 2-related factor 2 (Nrf2) via Keap1-dependent ubiquitination and proteasomal degradation or protein synthesis. Nrf2 is a transcription factor that regulates the cellular defense response. Most studies have focused on the effects of Nrf2 in tumor development. Here, the critical roles of Nrf2 in mouse early embryonic development were investigated. We found that brusatol treatment at the zygotic stage prevented the early embryo development. Most embryos stayed at the two-cell stage after 5 days of culture (P < 0.05). This effect was associated with the cell cycle arrest, as the mRNA level of CDK1 and cyclin B decreased at the two-cell stage after brusatol treatment. The embryo development potency was partially rescued by the injection of Nrf2 CRISPR activation plasmid. Thus, brusatol inhibited early embryo development by affecting Nrf2-related cell cycle transition from G2 to M phase that is dependent on cyclin B-CDK1 complex.
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Base de dados:
MEDLINE
Assunto principal:
Ciclo Celular
/
Desenvolvimento Embrionário
/
Fator 2 Relacionado a NF-E2
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article