The ABCs of sterol transport

Mammalian cells have developed various responses to minimize accumulation of unesterified cholesterol, as the latter can result in cell toxicity and death [reviewed in this edition by Björkhem (Björkhem, I. 2009. Are side-chain oxidized oxysterols regulators also in vivo? J. Lipid Res. In press)]. T...

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Bibliographic Details
Published in:Journal of lipid research 2009-04, Vol.50 Suppl, p.S80-S85
Main Authors: Baldán, Angel, Bojanic, Dragana D, Edwards, Peter A
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - genetics
Atherosclerosis - metabolism
ATP-Binding Cassette Transporters - classification
ATP-Binding Cassette Transporters - genetics
ATP-Binding Cassette Transporters - metabolism
Biological Transport
Homeostasis
Sterols - metabolism
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Summary:Mammalian cells have developed various responses to minimize accumulation of unesterified cholesterol, as the latter can result in cell toxicity and death [reviewed in this edition by Björkhem (Björkhem, I. 2009. Are side-chain oxidized oxysterols regulators also in vivo? J. Lipid Res. In press)]. These responses include esterification to sequester excess sterol in intracellular lipid droplets, repression of both cholesterol synthesis and LDL receptor expression (thus reducing endocytosis of LDL), and induction of a panoply of genes that promote sterol efflux and affect lipid metabolism. The nuclear receptor liver-X-receptor (LXR) functions as a cellular "sterol sensor" and plays a critical role in these latter transcriptional changes [reviewed in this edition by Glass (Shibata, N., and Glass C, K. 2009. Regulation of macrophage function in inflammation and atherosclerosis. J. Lipid Res. In press)]. Activation of LXR by either endogenous oxysterols or synthetic agonists induces the expression of many genes, including those encoding ATP-binding cassette (ABC) transporters ABCA1, ABCG1, ABCG5, and ABCG8. As discussed below, these four proteins function to promote sterol efflux from cells.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.R800044-JLR200