期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 274, 期 3, 页码 794-802出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.3243
关键词
ABCA1; nuclear receptors; ABC transporters; HDL; cholesterol efflux; oxysterols; macrophage
ATP-binding cassette transporter 1 (ABC1) mediates the active efflux of cholesterol from cells to apolipoproteins, To study the mechanisms of regulation of ABC1 gene expression, RAW 264.7 macrophages were transiently transfected with ABC1 promoter-luciferase reporter gene-fusion constructs. Transcription from a 1.64 kb fragment was induced by cholesterol loading but was not responsive to cAMP. Treatment of the cells with 9-cis retinoic acid or 20(S)-hydroxycholesterol, Ligands for the nuclear receptors LXR and RXR, resulted in a marked induction of luciferase expression. The responsible control element was mapped to an imperfect direct repeat of the nuclear receptor half-site TGACCT separated by four bases (DR-4) that binds LXR/RXR heterodimers, Endogenous ABC1 gene expression in RAW cells and apolipoprotein A-I mediated cholesterol efflux were also upregulated by both receptor ligands, These findings raise the possibility that ligands that activate the LXR-RXR heterodimer may be useful for the therapeutic modulation of the ABC1 pathway. (C) 2000 Academic Press.
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