PPARα and PPARδ Transactivity and p300 Binding Activity Induced by Arachidonic Acid in Colorectal Cancer Cell Line Caco-2

Abstract

It is reported that arachidonic acid strongly induces the conformational change in vitro and transactivity of PPARα in colorectal cancer cell line Caco-2. In this study, we demonstrated that the induction of conformational change and transactivity of PPARδ by arachidonic acid, as well as other polyunsaturated fatty acids, was considerably lower than that of PPARα. Mammalian two-hybrid assay showed that arachidonic acid enhanced binding of one of the coactivators, p300, to PPARα but not to PPARδ. Additionally, arachidonic acid induced in vitro binding of both PPARα-RXRα and PPARδ-RXRα heterodimers to several PPREs on CRBPII, L-FABP and ACO genes. Our results suggest that the lower transactivity of PPARδ for arachidonic acid in Caco-2 cells, compared with PPARα, is associated with the binding activity of p300 to the receptor.