PPAR alpha and PPAR delta transactivity and p300 binding activity induced by arachidonic acid in colorectal cancer cell line Caco-2.
It is reported that arachidonic acid strongly induces the conformational change in vitro and transactivity of PPAR alpha in colorectal cancer cell line Caco-2. In this study, we demonstrated that the induction of conformational change and transactivity of PPAR delta by arachidonic acid, as well as other polyunsaturated fatty acids, was considerably lower than that of PPAR alpha. Mammalian two-hybrid assay showed that arachidonic acid enhanced binding of one of the coactivators, p300, to PPAR alpha but not to PPAR delta. Additionally, arachidonic acid induced in vitro binding of both PPAR alpha-RXR alpha and PPAR delta-RXR alpha heterodimers to several PPREs on CRBPII, L-FABP and ACO genes. Our results suggest that the lower transactivity of PPAR delta for arachidonic acid in Caco-2 cells, compared with PPAR alpha, is associated with the binding activity of p300 to the receptor.
Mochizuki
Kazuki
K
Department of Nutrition, School and Nutritional Sciences, The University of Shizuoka, 51-1 Yada, Suruga, Shizuoka 422-8526, Japan.
Suzuki
Takuji
T
Goda
Toshinao
T
D016718:Arachidonic Acid / Q000494:pharmacology*; D018938:Caco-2 Cells; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D047493:PPAR alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011487:Protein Conformation; D014162:Transfection; D020798:Two-Hybrid System Techniques
D047493:PPAR alpha; D047494:PPAR delta; D016718:Arachidonic Acid; D019787:Linoleic Acid; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human