PT  - JOURNAL ARTICLE
AU  - Yongjun Wang
AU  - Pamela M. Rogers
AU  - Keith R. Stayrook
AU  - Chen Su
AU  - Gabor Varga
AU  - Qi Shen
AU  - Sunil Nagpal
AU  - Thomas P. Burris
TI  - The Selective Alzheimer's Disease Indicator-1 Gene (<em>Seladin-1/DHCR24</em>) Is a Liver X Receptor Target Gene
AID  - 10.1124/mol.108.048538
DP  - 2008 Dec 01
TA  - Molecular Pharmacology
PG  - 1716--1721
VI  - 74
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/74/6/1716.short
4100  - http://molpharm.aspetjournals.org/content/74/6/1716.full
SO  - Mol Pharmacol2008 Dec 01; 74
AB  - The nuclear hormone receptors liver X receptor α (LXRα) and LXRβ function as physiological receptors for oxidized cholesterol metabolites (oxysterols) and regulate several aspects of cholesterol and lipid metabolism. Seladin-1 was originally identified as a gene whose expression was down-regulated in regions of the brain associated with Alzheimer's disease. Seladin-1 has been demonstrated to be neuroprotective and was later characterized as 3β-hydroxysterol-Δ24 reductase (DHCR24), a key enzyme in the cholesterologenic pathway. Seladin-1 has also been shown to regulate lipid raft formation. In a whole genome screen for direct LXRα target genes, we identified an LXRα occupancy site within the second intron of the Seladin-1/DHCR24 gene. We characterized a novel LXR response element within the second intron of this gene that is able to confer LXR-specific ligand responsiveness to reporter gene in both HepG2 and human embryonic kidney 293 cells. Furthermore, we found that Seladin-1/DHCR24 gene expression is significantly decreased in skin isolated from LXRβ-null mice. Our data suggest that Seladin-1/DHCR24 is an LXR target gene and that LXR may regulate lipid raft formation. The American Society for Pharmacology and Experimental Therapeutics