PUBLICATION
Structure-dependent activities of polybrominated diphenyl ethers and hydroxylated metabolites on zebrafish retinoic acid receptor
- Authors
- Zhao, J., Zhu, X., Xu, T., Yin, D.
- ID
- ZDB-PUB-140801-16
- Date
- 2015
- Source
- Environmental science and pollution research international 22(3): 1723-30 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Biological Assay
- Endocrine Disruptors/chemistry
- Endocrine Disruptors/toxicity*
- Genes, Reporter
- Halogenated Diphenyl Ethers/chemistry*
- Halogenated Diphenyl Ethers/toxicity*
- Halogenation
- Hydroxylation
- Molecular Docking Simulation
- Molecular Structure
- Receptors, Retinoic Acid/metabolism*
- Transcription, Genetic/drug effects
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 25077655 Full text @ Environ. Sci. Pollut. Res. Int.
Citation
Zhao, J., Zhu, X., Xu, T., Yin, D. (2015) Structure-dependent activities of polybrominated diphenyl ethers and hydroxylated metabolites on zebrafish retinoic acid receptor. Environmental science and pollution research international. 22(3):1723-30.
Abstract
Polybrominated diphenyl ethers (PBDEs), a group of potential endocrine-disrupting chemicals (EDCs) have been shown to disrupt retinoid homeostasis in different species in both laboratory and field studies. However, the molecular mechanisms of interactions with the retinoic acid receptor (RAR) are not fully understood. Zebrafish have proven useful for investigating mechanisms of chemical toxicity. In the present study, a reporter gene assay was used to investigate the activities of 11 PBDEs and six OH-PBDEs with different degrees of bromination on zebrafish RAR. All tested OH-PBDEs induced RAR transcriptional activity; however, of the 11 PBDEs examined, only BDE28 and BDE154 affected the RAR transcriptional activity. Homology modeling and molecular docking were employed to simulate the interactions of PBDEs/OH-PBDEs with zebrafish RARs and to identify binding affinities to analyze the specialization of the interaction between RARs and PBDEs/OH-PBDEs. The results showed that although these compounds could bind with RARs, the effects of PBDEs/OH-PBDEs on RAR transcriptional activity did not depend on their RAR-binding abilities. The present study is the first attempt to demonstrate that OH-PBDEs could induce RAR transcriptional activity by binding directly with RAR; these effects are possibly related to the structure of the compounds, especially their hydroxylation and bromination. Most of the PBDEs could not directly interact with the RAR.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping