Details

Autor(en) / Beteiligte

• Zheng, Xiyue
• Ren, Xiao-Min
• Zhao, Lixia
• Guo, Liang-Hong

Titel

Binding and activation of estrogen related receptor γ as possible molecular initiating events of hydroxylated benzophenones endocrine disruption toxicity

Ist Teil von

• Environmental pollution (1987), 2020-08, Vol.263, p.114656, Article 114656

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• As a class of widely used ultraviolet filters, hydroxylated benzophenones (BPs) have been detected in various environmental and human samples, raising concerns about their ecological and health effects. BPs were found to impair reproductive functions, and their disruption effects on estrogen receptor, G protein-coupled estrogen receptor, and androgen receptor were investigated as possible mechanisms of action. In the present study, we investigated the binding and activation of estrogen related receptor γ (ERRγ) as an alternative mechanism of BPs reproductive toxicity. In competitive fluorescence binding assays, all of the 8 tested BPs were found to bind to the ligand-binding domain of ERRγ but with varying binding affinity. Molecular dock analysis indicated that binding of BPs to ERRγ in the agonistic conformation is preferred. In luciferase reporter gene assays in HepG2 cells, all the 8 BPs activated the transcription of ΕRRγ in a concentration-dependent manner in the range of 3–100 μM,consistent with the docking result. Hazard quotient calculation revealed a high risk on the BP-type personal care products users. The combined in vitro and in silico results suggest that binding and activation of ERRγ might be the molecular initiating events of an alternative mechanism of BPs endocrine disruption toxicity. [Display omitted] •Hydroxylated benzophenones (BPs) interact directly with estrogen related receptor γ (ERRγ) in vitro and in silico.•ERRγ transcriptional activity is enhanced by BPs which might lead to their endocrine disruption toxicity.•Exposure level of BP-type personal care product users is at high health risk.