Multidrug resistance P-glycoprotein is not involved in cholesterol esterification.
Biochem Biophys Res Commun
; 279(2): 369-77, 2000 Dec 20.
Article
en En
| MEDLINE
| ID: mdl-11118294
The aim of the present paper is to reinvestigate the role of multidrug resistance P-glycoprotein MDR1 and MDR-associated protein (MRP1) in cholesterol esterification using well-characterized inhibitors. Using specific substrate efflux assay, we show that GF120918 (0.2 microM) and probenecid (5 mM) were specific inhibitors of MDR1 and MRP1, respectively. In HepG2 cells, neither of them affect the esterification of cholesterol derived from the uptake of cholesterol-rich lipoprotein, while both verapamil (100 microM) and progesterone (100 microM) were able to inhibit cholesterol esterification. Similar results were obtained with verapamil, progesterone, and GF120918 in the MDR1-overexpressing cells MCF7/ADR. The capacity of progesterone to reduce cholesterol esterification is not correlated with its ability to inhibit MDR1 but is rather due to direct inhibition of acyl-CoA:cholesterol acyltransferase (ACAT). We conclude that the esterification of cholesterol is not correlated with MDR1 or MRP1 activity, thus excluding their role in the intracellular transport of endocytosis-derived cholesterol.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acridinas
/
Probenecid
/
Colesterol
/
Esterol O-Aciltransferasa
/
Ésteres del Colesterol
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Proteínas Asociadas a Resistencia a Múltiples Medicamentos
/
Tetrahidroisoquinolinas
/
Proteínas de Unión al ADN
/
Isoquinolinas
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2000
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos