Skip to main content

Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.

Publication ,  Journal Article
Fang, M; Webster, TF; Ferguson, PL; Stapleton, HM
Published in: Environmental health perspectives
February 2015

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 γ (PPARγ) nuclear receptor.Our goal was to determine the PPARγ 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.We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPARγ ligand-binding domain. Rosiglitazone was used as a positive control.Most of the tested compounds exhibited dose-dependent binding to PPARγ. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPARγ ligands. The most potent compound was 3-OH-BDE-47, with an IC50 (concentration required to reduce effect by 50%) of 0.24 μM. 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 PPARγ binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions.Our results suggest that several flame retardants are potential PPARγ ligands and that metabolism may lead to increased binding affinity. The PPARγ 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Environmental health perspectives

DOI

EISSN

1552-9924

ISSN

0091-6765

Publication Date

February 2015

Volume

123

Issue

2

Start / End Page

166 / 172

Related Subject Headings

  • Toxicology
  • Rats
  • PPAR gamma
  • Models, Chemical
  • Liver
  • Ligands
  • Hydrocarbons, Halogenated
  • Humans
  • Halogenated Diphenyl Ethers
  • Flame Retardants
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fang, M., Webster, T. F., Ferguson, P. L., & Stapleton, H. M. (2015). Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust. Environmental Health Perspectives, 123(2), 166–172. https://doi.org/10.1289/ehp.1408522
Fang, Mingliang, Thomas F. Webster, P Lee Ferguson, and Heather M. Stapleton. “Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.Environmental Health Perspectives 123, no. 2 (February 2015): 166–72. https://doi.org/10.1289/ehp.1408522.
Fang, Mingliang, et al. “Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.Environmental Health Perspectives, vol. 123, no. 2, Feb. 2015, pp. 166–72. Epmc, doi:10.1289/ehp.1408522.

Published In

Environmental health perspectives

DOI

EISSN

1552-9924

ISSN

0091-6765

Publication Date

February 2015

Volume

123

Issue

2

Start / End Page

166 / 172

Related Subject Headings

  • Toxicology
  • Rats
  • PPAR gamma
  • Models, Chemical
  • Liver
  • Ligands
  • Hydrocarbons, Halogenated
  • Humans
  • Halogenated Diphenyl Ethers
  • Flame Retardants