Isolation and characterization of unsaturated fatty acids as natural ligands for the retinoid-X receptor

被引：56

作者：

Goldstein, JT ^{[1
]}

Dobrzyn, A ^{[1
]}

Clagett-Dame, M ^{[1
]}

Pike, JW ^{[1
]}

DeLuca, HF ^{[1
]}

机构：

[1] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2003年 / 420卷 / 01期

关键词：

retinoid-X receptors; unsaturated fatty acids; ligands; nuclear receptors;

D O I：

10.1016/j.abb.2003.09.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The retinoid-X receptor (RXR) is a ligand activated nuclear receptor that is the heterodimer partner for many class 11 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 [H-3]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. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：185 / 193

页数：9

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