A simple method to screen ligands of peroxisome proliferator-activated receptor δ

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear receptor superfamily directly modulating gene expression by binding to specific ligands. Recently, it has been reported that PPAR delta ligands play an essential role in improvement of metabolic disorders and skin disorders. we introduce an enzyme-linked immunosorbent assay (ELISA) to screen new PPAR delta ligands. This method is based on the activation mechanism of PPAR delta where the ligand binding to PPAR delta induces the interaction of the receptor with transcriptional co-activators. We optimized a simple ELISA method for screening PPAR delta ligands. Among co-activators such as SRC-1, TIF-2, and p300, PPAR delta had more strong binding with SRC-1 in an ELISA system. GW501516 and linoleic acid, the well-known ligands of PPAR delta, increased the binding between PPAR delta and co-activators in a ligand dose-dependent manner. The recruitment of co-activator SRC-1 was also more effective than those of TIF-2 and p300. We optimized and developed a novel and useful ELISA system for the mass screening of PPAR delta ligands. This screening system may be useful in the development of drugs for metabolic disorders and skin disorders. (c) 2006 Elsevier B.V. All rights reserved.