Dexamethasone-induced apoptosis and up-regulation of Bim is dependent on glycogen synthase kinase-3.
Leuk Res
; 33(12): 1714-7, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19559478
ABSTRACT
Glucocorticoids are commonly used in the treatment of lymphoid malignancies. In this study, we show that apoptosis induced by dexamethasone (Dex), a synthetic glucocorticoid, was dependent on mitochondria, since overexpression of Bcl-X(L) prevented Dex-induced apoptotic changes. Dominant negative (DN) caspase-9 also prevented Dex-induced apoptotic changes including the loss of mitochondrial membrane potential indicating that caspase-9 controls mitochondrial changes. In addition, we evaluated the role of glycogen synthase kinase (GSK3) in Dex-induced apoptosis. Inhibition of GSK3 attenuated Dex-induced up-regulation of Bim, loss of mitochondrial membrane potential, release of cyt c and DNA fragmentation. These results indicate that GSK3 contributes to Dex-induced apoptosis by controlling up-regulation of Bim.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dexametasona
/
Regulação para Cima
/
Proteínas Proto-Oncogênicas
/
Apoptose
/
Quinase 3 da Glicogênio Sintase
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Proteínas Reguladoras de Apoptose
/
Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Finlândia