Binding and activity of bisphenol analogues to human peroxisome proliferator-activated receptor β/δ
| Autor: | Dong-Hui Zhang, Li-Dan Jiang, Yuan Qi, Chuanhai Li, Liang-Hong Guo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Bisphenol A
endocrine system Halogenation Bisphenol Health Toxicology and Mutagenesis Alpha (ethology) Peroxisome proliferator-activated receptor Bisphenol AF Environmental pollution chemistry.chemical_compound PPARβ/δ Phenols Humans GE1-350 PPAR alpha PPAR delta Benzhydryl Compounds Receptor chemistry.chemical_classification urogenital system Public Health Environmental and Occupational Health Transcriptional activity General Medicine Peroxisome Pollution Environmental sciences Molecular Docking Simulation chemistry Biochemistry Bisphenol analogues TD172-193.5 Tetrabromobisphenol A Binding potency hormones hormone substitutes and hormone antagonists |
| Zdroj: | Ecotoxicology and Environmental Safety, Vol 226, Iss, Pp 112849-(2021) |
| ISSN: | 1090-2414 |
| Popis: | Several studies have indicated metabolic function disruption effects of bisphenol analogues through peroxisome proliferator-activated receptor (PPAR) alpha and gamma pathways. In the present study, we found for the first time that PPARβ/δ might be a novel cellular target of bisphenol analogues. By using the fluorescence competitive binding assay, we found seven bisphenol analogues could bind to PPARβ/δ directly, among which tetrabromobisphenol A (TBBPA, 18.38-fold) and tetrachlorobisphenol A (TCBPA, 12.06-fold) exhibited stronger binding affinity than bisphenol A (BPA). In PPARβ/δ-mediated luciferase reporter gene assay, the seven bisphenol analogues showed transcriptional activity toward PPARβ/δ. Bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol B (BPB) even showed higher transcriptional activity than BPA, while TBBPA and TCBPA showed comparable activity with BPA. Moreover, in human liver HL-7702 cells, the bisphenol analogues promoted the expression of two PPARβ/δ target genes PDK4 and ANGPTL4. Molecular docking simulation indicated the binding potency of bisphenol analogues to PPARβ/δ might depend on halogenation and hydrophobicity and the transcriptional activity might depend on their binding affinity and hydrogen bond interactions. Overall, the PPARβ/δ pathway may provide a new mechanism for the metabolic function disruption of bisphenol analogues, and TBBPA and TCBPA might exert higher metabolic disruption effects than BPA via PPARβ/δ pathway. |
| Databáze: | OpenAIRE |
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