Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages

Gaus, Katharina and Kritharides, Leonard and Schmitz, Gerd and Boettcher, Alfred and Drobnik, Wolfgang and Langmann, Thomas and Quinn, Carmel M. and Death, Alison and Dean, Roger T. and Jessup, Wendy (2004) Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages. FASEB JOURNAL, 18 (1). 574-+. ISSN 0892-6638, 1530-6860

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Abstract

Cholesterol efflux to apolipoprotein A-1 (apoA-1) from cholesterol-loaded macrophages is an important anti -atheroscl erotic mechanism in reverse cholesterol transport. We recently provided kinetic evidence for two distinct pathways for cholesterol efflux to apoA-1 [Gaus et al. (2001) Biochemistry 40, 9363]. Cholesterol efflux from two membrane pools occurs sequentially with different kinetics; a small pool rapidly effluxed over the first hour, followed by progressive release from a major, slow efflux pool over several hours. In the present study, we propose that the rapid and slow cholesterol efflux pools represent cholesterol derived from lipid raft and nonraft domains of the plasma membrane, respectively. We provide direct evidence that apoA-1 binds to both lipid raft and nonraft domains of the macrophage plasma membrane. Conditions that selectively deplete plasma membrane lipid raft cholesterol, such as incorporation of 7-ketocholesterol or rapid exposure to cyclodextrins, block apoA-1 binding to these domains but also inhibit cholesterol efflux from the major, slow pool. We propose that cholesterol exported to apoA-1 from this major slow efflux pool derives from nonraft regions of the plasma membrane but that the interaction of apoA-1 with lipid rafts is necessary to stimulate this efflux.

Item Type: Article
Uncontrolled Keywords: LOW-DENSITY-LIPOPROTEIN; HUMAN THP-1 MACROPHAGES; CASSETTE TRANSPORTER 1; A-I; CELLULAR CHOLESTEROL; FOAM CELLS; ENDOPLASMIC-RETICULUM; PHOSPHOLIPID EFFLUX; LOADED MACROPHAGES; CAVEOLAE MEMBRANE; efflux; foam cell; reverse cholesterol transport; ABCA1; atherosclerosis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 Aug 2021 08:24
Last Modified: 04 Aug 2021 08:24
URI: https://pred.uni-regensburg.de/id/eprint/38160

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