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Titolo:
ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport
Autore:
Klucken, J; Buchler, C; Orso, E; Kaminski, WE; Porsch-Ozcurumez, M; Liebisch, C; Kapinsky, M; Diederich, W; Drobnik, W; Dean, M; Allikmets, R; Schmitz, G;
Indirizzi:
Univ Regensburg, Inst Clin Chem & Lab Med, D-93042 Regensburg, Germany Univ Regensburg Regensburg Germany D-93042 , D-93042 Regensburg, Germany NCI, Lab Genome Divers, Frederick, MD 21702 USA NCI Frederick MD USA 21702 CI, Lab Genome Divers, Frederick, MD 21702 USA Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA Columbia Univ New York NY USA 10032 pt Ophthalmol, New York, NY 10032 USA Columbia Univ, Dept Pathol, New York, NY 10032 USA Columbia Univ New YorkNY USA 10032 , Dept Pathol, New York, NY 10032 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 2, volume: 97, anno: 2000,
pagine: 817 - 822
SICI:
0027-8424(20000118)97:2<817:A(THHO>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-DENSITY-LIPOPROTEIN; FAMILIAL INTRAHEPATIC CHOLESTASIS; INTRACELLULAR CHOLESTEROL; MULTIDRUG-RESISTANCE; SIGNAL-TRANSDUCTION; BINDING PROTEINS; P-GLYCOPROTEIN; FIBROBLASTS; MEMBRANE; EFFLUX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Schmitz, G Univ Regensburg, Inst Clin Chem & Lab Med, Franz Josef Str Allee 11, D-93042 Regensburg, Germany Univ Regensburg Franz Josef Str Allee 11 Regensburg Germany D-93042
Citazione:
J. Klucken et al., "ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport", P NAS US, 97(2), 2000, pp. 817-822

Abstract

Excessive uptake of atherogenic lipoproteins such as modified low-density lipoprotein complexes by vascular macrophages leads to foam cell formation,a critical step in atherogenesis, Cholesterol afflux mediated by high-density lipoproteins (HDL) constitutes a protective mechanism against macrophage lipid overloading. The molecular mechanisms underlying this reverse cholesterol transport process are currently not fully understood. To identify effector proteins that are involved in macrophage lipid uptake and release, we searched for genes that are regulated during lipid influx and efflux in human macrophages using a differential display approach. We report here thatthe ATP-binding cassette (ABC) transporter ABCG1 (ABC8) is induced in monocyte-derived macrophages during cholesterol influx mediated by acetylated low-density lipoprotein. Conversely, lipid efflux in cholesterol-laden macrophages, mediated by the cholesterol acceptor HDL3, suppresses the expression of ABCG1, Immunocytochemical and flow cytometric analyses revealed that ABCG1 is expressed on the cell surface and in intracellular compartments of cholesterol-laden macrophages. Inhibition of ABCG1 protein expression usingan antisense strategy resulted in reduced HDL3-dependent efflux of cholesterol and choline-phospholipids. In a comprehensive analysis of the expression and regulation of all currently known human ABC transporters, we identified an additional set of ABC genes whose expression is regulated by cholesterol uptake or HDL3-mediated lipid release, suggesting a potential functionfor these transporters in macrophage lipid homeostasis. Our results demonstrating a regulator function for ABCG1 in cholesterol and phospholipid transport define a biologic activity for ABC transporters in macrophages.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 18:30:07