The retinoid X receptor enhances the function of the peroxisome proliferator activated receptor.
The peroxisome proliferator activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of non-genotoxic rodent hepatocarcinogens termed peroxisome proliferators. A key marker of peroxisome proliferator action is the peroxisomal enzyme acyl-CoA oxidase that is elevated about 10-fold in the liver of treated rodents. We have shown previously that a peroxisome proliferator response element (PPRE) is located 570 bp upstream of the rat acyl-CoA oxidase gene and that PPAR binds to it. We show here that the retinoid X receptor (RXR) is required for PPAR to bind to the PPRE and that the RXR ligand, 9-cis retinoic acid, enhances PPAR action. These results therefore suggest that retinoids may modulate the action of peroxisome proliferators.
ZENECA Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
I
I
Issemann
R A
RA
Prince
J D
JD
Tugwood
S
S
Green
D042962:Acyl-CoA Oxidase; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D002460:Cell Line; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors
D002273:Carcinogens; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase