PUBLICATION
INTEGRATED IN SILICO AND IN VIVO APPROACHES TO INVESTIGATE EFFECTS OF BDE-99 MEDIATED BY THE NUCLEAR RECEPTORS ON DEVELOPING ZEBRAFISH
- Authors
- Zhang, L., Jin, Y., Han, Z., Liu, H., Shi, L., Hua, X., A Doering, J., Tang, S., P Giesy, J., Yu, H.
- ID
- ZDB-PUB-171016-7
- Date
- 2017
- Source
- Environmental toxicology and chemistry 37(3): 780-787 (Journal)
- Registered Authors
- Keywords
- Aryl hydrocarbon receptor (AhR), Cross-talk, Docking, Molecular dynamic (MD) simulation, Pregnane X receptor (PXR)
- MeSH Terms
-
- Animals
- Binding Sites
- Computer Simulation*
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects
- Gene Regulatory Networks/drug effects
- Halogenated Diphenyl Ethers/toxicity*
- Molecular Docking Simulation
- Molecular Dynamics Simulation
- Receptors, Cytoplasmic and Nuclear/metabolism*
- Transcription, Genetic/drug effects
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 29027256 Full text @ Environ. Toxicol. Chem.
Citation
Zhang, L., Jin, Y., Han, Z., Liu, H., Shi, L., Hua, X., A Doering, J., Tang, S., P Giesy, J., Yu, H. (2017) INTEGRATED IN SILICO AND IN VIVO APPROACHES TO INVESTIGATE EFFECTS OF BDE-99 MEDIATED BY THE NUCLEAR RECEPTORS ON DEVELOPING ZEBRAFISH. Environmental toxicology and chemistry. 37(3):780-787.
Abstract
BDE-99 is one of the most abundant PBDEs, which due to its potential persistence and bioaccumulation occurs in aquatic wildlife. Previous studies in mammals have shown that BDE-99 affected development and disrupted certain endocrine functions through signaling pathways mediated by nuclear receptors (NRs). However, fewer studies have investigated the potential of BDE-99 to interact with NRs in aquatic vertebrates, such as fish. In the present study, interactions between BDE-99 and NRs were investigated by use of in silico and in vivo approaches. BDE-99 could dock into ligand binding domain (LBD) of zebrafish aryl hydrocarbon receptor 2 (AhR2) and pregnane X receptor (PXR). BDE-99 had a significant effect on transcriptional profiles of genes associated with AhR or PXR. Based on the developed cytoscape of all zebrafish genes, it was also inferred that AhR and PXR could interact via cross-talk. In addition, both in silico and in vivo results found BDE-99 affected peroxisome proliferator activated receptor alpha (PPARĪ±), glucocorticoid receptor (GR) and thyroid receptor (TR). Collectively, the results presented here demonstrated, for the first time, detailed in silico evidences that BDE-99 could bind to and interact with zebrafish AhR and PXR. These findings can be used to elaborate the molecular mechanism of BDE-99 and guide more objective environmental risk assessments. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping