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ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis.
- Source :
-
Cell metabolism [Cell Metab] 2013 Aug 06; Vol. 18 (2), pp. 225-38. - Publication Year :
- 2013
-
Abstract
- ABCA12 is involved in the transport of ceramides in skin, but it may play a wider role in lipid metabolism. We show that, in Abca12-deficient macrophages, cholesterol efflux failed to respond to activation with LXR agonists. Abca12 deficiency caused a reduction in the abundance of Abca1, Abcg1, and Lxrβ. Overexpression of Lxrβ reversed the effects. Mechanistically, Abca12 deficiency did not affect expression of genes involved in cholesterol metabolism. Instead, a physical association between Abca1, Abca12, and Lxrβ proteins was established. Abca12 deficiency enhanced interaction between Abca1 and Lxrβ and the degradation of Abca1. Overexpression of ABCA12 in HeLa-ABCA1 cells increased the abundance and stability of ABCA1. Abca12 deficiency caused an accumulation of cholesterol in macrophages and the formation of foam cells, impaired reverse cholesterol transport in vivo, and increased the development of atherosclerosis in irradiated Apoe(-/-) mice reconstituted with Apoe(-/-)Abca12(-/-) bone marrow. Thus, ABCA12 regulates the cellular cholesterol metabolism via an LXRβ-dependent posttranscriptional mechanism.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters deficiency
Animals
Atherosclerosis genetics
Atherosclerosis metabolism
Biological Transport genetics
Cell Line
Foam Cells metabolism
HeLa Cells
Humans
Lipid Metabolism genetics
Lipoproteins metabolism
Liver X Receptors
Mice
Mice, Inbred C57BL
Mice, Transgenic
Orphan Nuclear Receptors biosynthesis
ATP Binding Cassette Transporter 1 metabolism
ATP-Binding Cassette Transporters metabolism
Cholesterol metabolism
Macrophages metabolism
Orphan Nuclear Receptors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7420
- Volume :
- 18
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 23931754
- Full Text :
- https://doi.org/10.1016/j.cmet.2013.07.003