title: A simple method to screen ligands of peroxisome proliferator-activated receptor delta.
abstract: 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 PPARdelta ligands play an essential role in improvement of metabolic disorders and skin disorders. We introduce an enzyme-linked immunosorbent assay (ELISA) to screen new PPARdelta ligands. This method is based on the activation mechanism of PPARdelta where the ligand binding to PPARdelta induces the interaction of the receptor with transcriptional co-activators. We optimized a simple ELISA method for screening PPARdelta ligands. Among co-activators such as SRC-1, TIF-2, and p300, PPARdelta had more strong binding with SRC-1 in an ELISA system. GW501516 and linoleic acid, the well-known ligands of PPARdelta, increased the binding between PPARdelta 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 PPARdelta ligands. This screening system may be useful in the development of drugs for metabolic disorders and skin disorders.
authors.affiliation: Department of Bioscience & Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Cho
authors.forename: Hyo-Eun
authors.initials: HE
authors.lastname: Yoon
authors.forename: Jeong-Woo
authors.initials: JW
authors.lastname: Kang
authors.forename: Se-Won
authors.initials: SW
authors.lastname: Park
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Jin-Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Song
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D003001:Cloning, Molecular; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D050881:E1A-Associated p300 Protein / Q000737:chemistry / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D056920:Nuclear Receptor Coactivator 1; D047494:PPAR delta / Q000378:metabolism*; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D047494:PPAR delta; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1