Klucken, J and Buchler, C and Orso, E and Kaminski, WE and Porsch-Ozcurumez, M and Liebisch, C and Kapinsky, M and Diederich, W and Drobnik, W and Dean, M and Allikmets, R and Schmitz, G (2000) ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 97 (2). pp. 817-822. ISSN 0027-8424,
Full text not available from this repository.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 that the 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 using an 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 function for 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH-DENSITY-LIPOPROTEIN; FAMILIAL INTRAHEPATIC CHOLESTASIS; INTRACELLULAR CHOLESTEROL; MULTIDRUG-RESISTANCE; SIGNAL-TRANSDUCTION; BINDING PROTEINS; P-GLYCOPROTEIN; FIBROBLASTS; MEMBRANE; EFFLUX; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 May 2021 10:22 |
| Last Modified: | 19 May 2021 10:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42890 |
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