Abstract
The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Biological Assay
-
Brain / growth & development
-
Brain / metabolism
-
Brain Chemistry*
-
Cell Line
-
Chromatography, High Pressure Liquid
-
Culture Media, Conditioned
-
Dimerization
-
Docosahexaenoic Acids / isolation & purification*
-
Docosahexaenoic Acids / metabolism*
-
Docosahexaenoic Acids / pharmacology
-
Fatty Acids, Unsaturated / pharmacology
-
Histone Acetyltransferases
-
Humans
-
Ligands
-
Male
-
Mice
-
Nuclear Receptor Coactivator 1
-
Receptors, Retinoic Acid / genetics
-
Receptors, Retinoic Acid / metabolism*
-
Recombinant Fusion Proteins / metabolism
-
Retinoid X Receptors
-
Signal Transduction
-
Spectrometry, Mass, Electrospray Ionization
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
-
Transfection
-
Tumor Cells, Cultured
Substances
-
Culture Media, Conditioned
-
Fatty Acids, Unsaturated
-
Ligands
-
Receptors, Retinoic Acid
-
Recombinant Fusion Proteins
-
Retinoid X Receptors
-
Transcription Factors
-
Docosahexaenoic Acids
-
Histone Acetyltransferases
-
NCOA1 protein, human
-
Ncoa1 protein, mouse
-
Nuclear Receptor Coactivator 1