title: Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.
abstract: Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025× equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.
authors.forename: Jianxian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.
authors.forename: Hattan A
authors.initials: HA
authors.lastname: Alharbi
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.|School of Environment and Sustainability, 117 Science Place, Saskatoon, Saskatchewan Canada , S7N 5C8.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.|Department of Veterinary Biomedical Sciences, University of Saskatchewan , Saskatoon, Saskatchewan Canada S7N 5B3.|Zoology Department, Center for Integrative Toxicology, Michigan State University , East Lansing, Michigan 48824, United States.|State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, People's Republic of China.|School of Biology, University of Hong Kong , Hong Kong, SAR China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.
authors.forename: Steve
authors.initials: S
authors.lastname: Wiseman
mesh_terms: D050156:Adipogenesis; D008024:Ligands; D061329:Oil and Gas Fields; D047495:PPAR gamma / Q000378:metabolism*; D014867:Water
chemical_list: D008024:Ligands; D047495:PPAR gamma; D014867:Water