Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.

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Murakami K, Ide T, Suzuki M, Mochizuki T, Kadowaki T

Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.

Biochem Biophys Res Commun. 1999 Jul 14;260(3):609-13.

PubMed ID
10403814 [ View in PubMed
]
Abstract

The alpha isoform of peroxisome proliferators-activated receptor (PPAR) is activated by fatty acids, their metabolites, and the fibrate class of lipid-lowering agents. To test the ability of these activators to directly bind the ligand-binding domain of human PPARalpha, we performed a competitive binding assay using radiolabeled [(3)H]KRP-297, a known ligand for human PPARalpha. Long-chain fatty acids and eicosanoids were even more potent ligands for human PPARalpha than the hitherto most potent PPARalpha ligand WY-14,643. Moreover, these natural ligands avidly activated this receptor in a transient transcriptional assay. This study provides the direct evidence that human PPARalpha is activated through the direct binding of fatty acids and eicosanoids, as well as of a fibrate, to its ligand-binding domain.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
alpha-Linolenic acidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
Arachidonic AcidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
IcosapentPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
Lauric acidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
Myristic acidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
Oleic AcidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
Palmitic AcidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails
Stearic acidPeroxisome proliferator-activated receptor alphaProteinHumans
Unknown
Not AvailableDetails