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- W2116875174 abstract "A cell-based transactivation assay was established using the mouse full-length peroxisome proliferator-activated receptor (PPAR) cDNA sequence and the positive peroxisome proliferator-responsive regulatory element (-578 to -553) of the rat acyl-CoA oxidase gene promoter. Activation of the reporter plasmid was dependent on co-transfection of the full-length PPAR cDNA, and the response was greatly stimulated, up to 100-fold, by peroxisome proliferators such as Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid), nafenopin (2-methyl-2[p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]-propionic acid), and clofibric acid (2-([p]-chlorophenoxy)-2-methylpropionic acid). Activation of the reporter plasmid promoter by the full-length PPAR cDNA also occurred at peroxisomal proliferator concentrations 40 times lower than that required for similar stimulation by a glucocorticoid-PPAR chimeric receptor. By using the stereoisomers of MK-571 ((+-)-3-(((3-(2-(7-chloro-2-quinolinyl)ethenyl)-phenyl)((3- (dimethylamino)-3-oxopropyl)-thio)methyl)-thio)propanoic acid), a potent leukotriene D4 receptor antagonist, we could show enantioselective activation of PPAR. The use of this compound in mice results in peroxisome proliferation; however, nearly all of the peroxisome proliferating activity can be attributed to the S enantiomer. Our results show a similar enantiomeric discrimination in PPAR activation of the reporter plasmid promoter, where again most of the activity can be attributed to the S enantiomer. The equivalent activities of these stereoisomers both in vivo and in the PPAR transactivation assay strongly implicate PPAR as a major component of the peroxisome proliferating mechanism in rodents." @default.
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- W2116875174 date "1993-03-01" @default.
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- W2116875174 title "Enantioselective activation of the peroxisome proliferator-activated receptor." @default.
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- W2116875174 doi "https://doi.org/10.1016/s0021-9258(18)53353-6" @default.
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