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Molecular Pharmacology Fast Forward
First published on September 24, 2008; DOI: 10.1124/mol.108.048538


0026-895X/08/7406-1716-1721$20.00
Mol Pharmacol 74:1716-1721, 2008

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The Selective Alzheimer's Disease Indicator-1 Gene (Seladin-1/DHCR24) Is a Liver X Receptor Target Gene

Yongjun Wang1, Pamela M. Rogers, Keith R. Stayrook, Chen Su, Gabor Varga, Qi Shen, Sunil Nagpal, and Thomas P. Burris1

Nuclear Receptor Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana (Y.W., P.M.R., T.P.B.); Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana (K.R.S., C.S., G.V.); and Wyeth Research, Collegeville, Pennsylvania (Q.S., S.N.)

The nuclear hormone receptors liver X receptor {alpha} (LXR{alpha}) 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-{Delta}24 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 LXR{alpha} target genes, we identified an LXR{alpha} 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.


Received for publication May 1, 2008.

Accepted for publication September 24, 2008.

Address correspondence to: Dr. Thomas P. Burris, The Scripps Research Institute, 5353 Parkside Dr., Jupiter, FL 33458. E-mail: tburris{at}scripps.edu







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