Ceramide synthesis correlates with the posttranscriptional regulation of the sterol-regulatory element-binding protein.
Arterioscler Thromb Vasc Biol
; 24(5): 943-8, 2004 May.
Article
en En
| MEDLINE
| ID: mdl-15132973
OBJECTIVE: Sterol-regulatory element-binding proteins (SREBPs) regulate transcription of genes of lipid metabolism. Ceramide decreases transcriptionally active SREBP levels independently of intracellular cholesterol levels. Mechanisms of the ceramide-mediated decrease of SREBP levels were investigated. METHODS AND RESULTS: Experiments were performed in Chinese hamster ovary cells. Inhibition of ceramide synthesis with myriocin, cycloserine, or fumonisin decreases levels of transcriptionally active SREBP and reduces SRE-mediated gene transcription. When ceramide synthesis is increased through exogenous sphingosine or inhibition of sphingosine kinase, SRE-mediated gene transcription is increased. The important role of ceramide synthesis in SRE-mediated gene transcription is confirmed in LY-B cells that do not synthesize ceramide de novo. LY-B cells fail to increase SRE-mediated gene transcription in sterol depletion. CONCLUSIONS: Ceramide synthesis correlates with the generation of transcriptionally active SREBP and SRE-mediated gene transcription. Inhibition of ceramide synthesis decreases levels of transcriptionally active SREBP and SRE-mediated gene transcription. It is hypothesized that the process of ongoing ceramide synthesis contributes to the physiological processing of SREBP, perhaps affecting ER-to-Golgi trafficking. Taken together, modification of ceramide synthesis could be a novel target for drug development in the pharmacologic modification of SRE-dependent pathways.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esfingosina
/
Factores de Transcripción
/
Transcripción Genética
/
Ceramidas
/
Procesamiento Postranscripcional del ARN
/
1-Desoxinojirimicina
/
Proteínas Potenciadoras de Unión a CCAAT
/
Proteínas de Unión al ADN
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos