Phytanic Acid is a Retinoid X Receptor Ligand
Open Access
- 1 February 1996
- journal article
- Published by Wiley in European Journal of Biochemistry
- Vol. 236 (1), 328-333
- https://doi.org/10.1111/j.1432-1033.1996.00328.x
Abstract
Metabolic defects in phytanic acid catabolism have been shown to be connected with a number of human diseases which can lead to lethal defects of the nervous system and other organs. These effects are probably a result of the very high accumulation of phytanic acid in tissues throughout the body, due to defects in phytanic acid oxidation, the peroxisome being a major site for this process. The nuclear hormone receptors peroxisome proliferator-activated receptor and retinoid X receptor (RXR) have been shown to function as transcription factors in the control of the peroxisomal enzyme expression. Known activators of peroxisome proliferator-activated receptor include polyunsaturated fatty acids and, for RXR, the 9-cis isomer of retinoic acid. Here we report that phytanic acid is also a natural ligand for RXRα, being able to activate a RXR-responsive promoter. We present evidence that phytanic acid binds to RXRα, promotes formation of an RXRα/RXR response element complex (as detected by gel retardation), and induces a RXRα conformational change similar to that induced by 9-cis-retinoic acid (as detected by protease sensitivity). These results suggest an involvement of RXRα in the control of fatty acid metabolism and could imply that RXRs have a role in the disease effects resulting from defective phytanic acid catabolism.Keywords
This publication has 24 references indexed in Scilit:
- Update on genetic and molecular investigations of diseases with general impairment of peroxisomal functionsBiochimie, 1993
- Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptorsNature, 1992
- Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.Proceedings of the National Academy of Sciences, 1992
- 9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRαNature, 1992
- Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferatorsNature, 1990
- The fatty acid composition of skin and plasma lipids in Refsum's diseaseClinica Chimica Acta; International Journal of Clinical Chemistry, 1978
- The presence of phytanic acid in normal human and animal plasmaBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1966
- 3,7,11, 15-Tetramethylhexadecanoic acid: ITs occurrence in the tissues of humans afflicted with refsum's syndromeBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1965
- Conversion of U-C14-phytol to phytanic acid and its oxidation in heredopathia atactica polyneuritiformisBiochemical and Biophysical Research Communications, 1965
- Über das Vorkommen der 3.7.11.15-Tetramethyl-hexadecansäure (Phytansäure) in den Cholesterinestern und anderen Lipoidfraktionen der Organe bei einem Krankheitsfall unbekannter Genese (Verdacht auf Heredopathia atactica polyneuritiformis [Refsum-Syndrom])Hoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1963