5-(3,5-Di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione modulates peroxisome proliferators-activated receptor gamma in 3T3-L1 adipocytes: roles as a PPARgamma ligand.
Based on the binding between peroxisome proliferators-activated receptor gamma (PPARgamma) and steroid receptor co-activator-1 (SRC-1), an enzyme-linked immunosorbent assay (ELISA) was used to screen new PPARgamma ligands from various benzylidinethiazole derivatives, which have anti-inflammatory activity. Among those derivatives, 5-(3,5-di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione (BTZD) increased the binding between PPARgamma and SRC-1. BTZD was found to induce adipogenesis and PPARgamma trans-activation in 3T3-L1 pre-adipocyte, and increased the binding between PPARgamma and SRC-1 in in vitro binding assay and complex consisting of PPARgamma and SRC-1 in the co-immunoprecipitaion. Chromatin immunoprecipitation (ChIP) analysis revealed that BTZD induced the binding of PPARgamma-SRC-1 complex to PPAR response element (PPRE) in the same pattern of other PPARgamma ligand. From these studies, we have identified and studied the function of a new PPARgamma ligand, BTZD. We suggest that BTZD can be used as a modulator of PPARgamma. This study applying ELISA and ChIP assay can offer new methods to screen PPARgamma ligand and understand the effects of PPARgamma ligands on inflammation.
Cho
Min-Chul
MC
Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Daejeon 305-600, Republic of Korea.
Lee
Woo Song
WS
Hong
Jin-Tae
JT
Park
Se-Won
SW
Moon
Dong-Cheul
DC
Paik
Sang-Gi
SG
Yoon
Do-Young
DY
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D056920:Nuclear Receptor Coactivator 1; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins; D045162:Thiazolidinediones / Q000378:metabolism* / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
C507175:5-(3,5-di-tert-butyl-4-hydroxybenzylidene)thiazolidine-2,4-dione; D008024:Ligands; D047495:PPAR gamma; D011993:Recombinant Fusion Proteins; D045162:Thiazolidinediones; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1