Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain.
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.
de Urquiza
A M
AM
Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, S-171 77 Stockholm, Sweden.
Liu
S
S
Sjöberg
M
M
Zetterström
R H
RH
Griffiths
W
W
Sjövall
J
J
Perlmann
T
T
D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D001923:Brain Chemistry; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D019281:Dimerization; D004281:Docosahexaenoic Acids / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D056920:Nuclear Receptor Coactivator 1; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D015398:Signal Transduction; D021241:Spectrometry, Mass, Electrospray Ionization; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D005231:Fatty Acids, Unsaturated; D008024:Ligands; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004281:Docosahexaenoic Acids; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1