Biochem Biophys Res Commun. 2000 Dec 20;279(2):369-77.

Multidrug resistance P-glycoprotein is not involved in cholesterol esterification.

Source

Laboratoire GlaxoWellcome, Centre de Recherches, 25 Avenue du Quebec, les Ulis Cedex, 91951, France. mi18785@GlaxoWellcome.co.uk

Abstract

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.

PMID:: 11118294; [PubMed - indexed for MEDLINE]

MeSH Terms, Substances

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Labome Researcher Resource - ExactAntigen/Labome

Medical

Cholesterol - MedlinePlus Health Information

Molecular Biology Databases

Supplemental Content

Save items

Related citations in PubMed

Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma membrane cholesterol. [J Biol Chem. 1999]
Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma membrane cholesterol.
Luker GD, Nilsson KR, Covey DF, Piwnica-Worms D. J Biol Chem. 1999 Mar 12; 274(11):6979-91.
Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. [Anticancer Drugs. 1997]
Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP.
Germann UA, Ford PJ, Shlyakhter D, Mason VS, Harding MW. Anticancer Drugs. 1997 Feb; 8(2):141-55.
Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). [Drug Metab Dispos. 2002]
Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT).
Guo A, Marinaro W, Hu P, Sinko PJ. Drug Metab Dispos. 2002 Apr; 30(4):457-63.
Review [Involvement of phospholipase A2 in the supply of fatty acids required for cholesterol esterification associated with uptake of oxidized low-density lipoprotein in macrophages]. [Yakugaku Zasshi. 2003]
Review [Involvement of phospholipase A2 in the supply of fatty acids required for cholesterol esterification associated with uptake of oxidized low-density lipoprotein in macrophages].
Akiba S. Yakugaku Zasshi. 2003 Oct; 123(10):845-53.
Review Development of multidrug-resistance convertors: sense or nonsense? [Invest New Drugs. 2000]
Review Development of multidrug-resistance convertors: sense or nonsense?
van Zuylen L, Nooter K, Sparreboom A, Verweij J. Invest New Drugs. 2000 Aug; 18(3):205-20.

See reviews... See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Compound
PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance
PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

Recent activity

Clear Turn Off Turn On

Multidrug resistance P-glycoprotein is not involved in cholesterol esterificatio...
Multidrug resistance P-glycoprotein is not involved in cholesterol esterification.
Biochem Biophys Res Commun. 2000 Dec 20 ;279(2):369-77.

PubMed
Additional educational needs in children born to mothers with epilepsy.
Additional educational needs in children born to mothers with epilepsy.
J Neurol Neurosurg Psychiatry. 2001 Jan ;70(1):15-21.

PubMed
Sequential action of two GTPases to promote vacuole docking and fusion.
Sequential action of two GTPases to promote vacuole docking and fusion.
EMBO J. 2000 Dec 15 ;19(24):6713-20.

PubMed
Arabidopsis transcription factors: genome-wide comparative analysis among eukary...
Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.
Science. 2000 Dec 15 ;290(5499):2105-10.

PubMed
Simultaneous quantitation of the 5'-triphosphate metabolites of zidovudine, lami...
Simultaneous quantitation of the 5'-triphosphate metabolites of zidovudine, lamivudine, and stavudine in peripheral mononuclear blood cells of HIV infected patients by high-performance liquid chromatography tandem mass spectrometry.
J Am Soc Mass Spectrom. 2000 Dec ;11(12):1134-43.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: