Isolation and characterization of unsaturated fatty acids as natural ligands for the retinoid-X receptor.
The retinoid-X receptor (RXR) is a ligand activated nuclear receptor that is the heterodimer partner for many class II nuclear receptors. Previously identified natural ligands for this receptor include 9-cis retinoic acid (9cRA), docosahexaenoic acid, and phytanic acid. Our studies were performed to determine if there are any unidentified, physiologically important RXR ligands. Agonists for RXR were purified from rat heart and testes lipid extracts with the use of a cell-based reporter assay to monitor RXR activation. Purified active fractions contained a variety of unsaturated fatty acids and components were quantified by gas-liquid chromatography of derivatized samples. The corresponding fatty acid standards elicited a similar response in the reporter cell assay. Competition binding analysis revealed that the active fatty acids compete with [3H]9cRA for binding to RXR. Non-esterified fatty acids were analyzed from lipid extracts of isolated heart and testes nuclei and endogenous concentrations were found to be within the range of their determined binding affinities. Our studies reveal tissue dependent profiles of RXR agonists and support the idea of unsaturated fatty acids as physiological ligands of RXR.
Goldstein
Jonathan T
JT
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dobrzyn
Agnieszka
A
Clagett-Dame
Margaret
M
Pike
J Wesley
JW
DeLuca
Hector F
HF
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism*; D047488:Retinoid X Receptors; D013737:Testis / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
D005231:Fatty Acids, Unsaturated; D008024:Ligands; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors