Growth differentiation factor-15 induces expression of ATP-binding cassette transporter A1 through PI3-K/PKCζ/SP1 pathway in THP-1 macrophages.
Biochem Biophys Res Commun
; 444(3): 325-31, 2014 Feb 14.
Article
en En
| MEDLINE
| ID: mdl-24462860
ABSTRACT
OBJECTIVE:
The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase Cζ (PKCζ)/specificity protein 1 (SP1) pathway in THP-1 macrophages. METHODS ANDRESULTS:
We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKCζ and SP1, respectively, suggesting the potential roles of PI3K, PKCζ and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKCζ and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation.CONCLUSION:
Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKCζ/SP1 signaling pathway and enhancing cholesterol efflux.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Factor de Transcripción Sp1
/
Factor 15 de Diferenciación de Crecimiento
/
Fosfatidilinositol 3-Quinasa
/
Transportador 1 de Casete de Unión a ATP
/
Macrófagos
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2014
Tipo del documento:
Article
País de afiliación:
China