The selective Alzheimer's disease indicator-1 gene (Seladin-1/DHCR24) is a liver X receptor target gene

Yongjun Wang, Pamela M. Rogers, Keith R. Stayrook, Chen Su, Gabor Varga, Qi Shen, Sunil Nagpal, Thomas P. Burris

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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-Δctase (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.

Original languageEnglish (US)
Pages (from-to)1716-1721
Number of pages6
JournalMolecular pharmacology
Volume74
Issue number6
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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