title: Activation of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) by Semi-Volatile Compounds (SVOCs) and Chemical Mixtures in Indoor Dust.
abstract: Recently, we reported that several semi-volatile compounds (SVOCs) were competitive ligands for human peroxisome proliferator-activated nuclear receptor gamma (PPARγ1). We also observed significant binding from chemicals extracted from house dust at a concentration of 3 mg dust/mL in the dosing medium. To follow up on this study, a commercially available reporter gene assay (GeneBLAzer PPARγ1 non-DA Assay, Invitrogen) was used to investigate the PPARγ1 activation by 30 common SVOCs (e.g., brominated flame retardants, organophosphates, and phthalates) and in house dust extracts. Twenty-eight SVOCs or their metabolites were either confirmed or for the first time were found to be weak or moderate PPARγ1 agonists. We also observed activation in 15 of 25 dust extracts examined. In some cases, activation was as high as 50% of the activation of the positive control (rosiglitazone). Furthermore, there was a significant and positive correlation (r = 0.7, p < 0.003) between data collected from this reporter assay and our previous ligand binding assay tested on the same dust extracts. Our results suggest that many SVOCs ubiquitous in house dust, or their metabolites, are possible PPARγ1 agonists. Also, chemical mixtures present in house dust at environmentally relevant levels can activate human PPARγ1 in a transfected cell culture system, and further research is needed to identify the primary chemical(s) driving this activity.
authors.affiliation: †Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Fang
authors.affiliation: ‡Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts 02118, United States.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Webster
authors.affiliation: †Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
mesh_terms: D016902:Air Pollution, Indoor / Q000032:analysis*; D001681:Biological Assay; D004391:Dust / Q000032:analysis*; D017930:Genes, Reporter; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology; D008024:Ligands; D010755:Organophosphates / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism*; D055549:Volatile Organic Compounds / Q000494:pharmacology*
chemical_list: D004391:Dust; D006846:Hydrocarbons, Halogenated; D008024:Ligands; D010755:Organophosphates; D047495:PPAR gamma; D055549:Volatile Organic Compounds