Characterizing the peroxisome proliferator-activated receptor (PPARgamma) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.
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Fang M, Webster TF, Ferguson PL, Stapleton HM
Characterizing the peroxisome proliferator-activated receptor (PPARgamma) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.
Environ Health Perspect. 2015 Feb;123(2):166-72. doi: 10.1289/ehp.1408522. Epub 2014 Oct 14.
- PubMed ID
- 25314719 [ View in PubMed]
- Abstract
BACKGROUND: Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor gamma (PPARgamma) nuclear receptor. OBJECTIVES: Our goal was to determine the PPARgamma ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated. METHODS: We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPARgamma ligand-binding domain. Rosiglitazone was used as a positive control. RESULTS: Most of the tested compounds exhibited dose-dependent binding to PPARgamma. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPARgamma ligands. The most potent compound was 3-OH-BDE-47, with an IC50 (concentration required to reduce effect by 50%) of 0.24 muM. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3-16% increase in PPARgamma binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions. CONCLUSION: Our results suggest that several flame retardants are potential PPARgamma ligands and that metabolism may lead to increased binding affinity. The PPARgamma binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Triclosan Peroxisome proliferator-activated receptor gamma Protein Humans UnknownNot Available Details