SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling.
Biochem Biophys Res Commun
; 479(1): 54-60, 2016 10 07.
Article
em En
| MEDLINE
| ID: mdl-27614310
ABSTRACT
Dexamethasone (Dex) causes osteoblast cell injuries. In the present research, we tested the potential effect of SC79, a novel and specific Akt activator, against Dex in osteoblasts. In primary murine osteoblasts and osteoblastic MC3T3-E1 cells, pretreatment with SC79 significantly attenuated Dex-induced cell death. Further, Dex-induced mitochondrial permeability transition pore (mPTP) opening, cytochrome C release and apoptosis activation were dramatically alleviated with SC79 pretreatment in above cells. At the molecular level, SC79 activated Akt, which was indispensable for subsequent osteoblast protection against Dex. Akt inhibitors (LY294002, perifosine and MK-2206) blocked SC79-induced Akt activation and abolished its anti-Dex actions in osteoblasts. Further, SC79 activated Akt downstream Nrf2 (NF-E2-related factor 2) signaling and attenuated Dex-induced oxidative stress in osteoblasts. Nrf2 shRNA knockdown or S40T mutation almost reversed SC79-mediated anti-oxidant and cytoprotective activities in osteoblasts. Together, these results suggest that SC79 activates Akt-Nrf2 signaling to protect osteoblasts from Dex.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Benzopiranos
/
Dexametasona
/
Transdução de Sinais
/
Proteínas Proto-Oncogênicas c-akt
/
Fator 2 Relacionado a NF-E2
/
Acetatos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China