PUBLICATION
In vitro biolayer interferometry analysis of acetylcholinesterase as a potential target of aryl-organophosphorus flame-retardants
- Authors
- Shi, Q., Guo, W., Shen, Q., Han, J., Lei, L., Chen, L., Yang, L., Feng, C., Zhou, B.
- ID
- ZDB-PUB-210120-14
- Date
- 2020
- Source
- Journal of hazardous materials 409: 124999 (Journal)
- Registered Authors
- Yang, LiHua, Zhou, BingSheng
- Keywords
- Acetylcholinesterase (AChE), Biolayer interferometry, Molecular docking, Neurotoxicity, Organophosphorus flame retardants, Zebrafish larvae
- MeSH Terms
-
- Acetylcholinesterase
- Animals
- Flame Retardants*/toxicity
- Interferometry
- Molecular Docking Simulation
- Organophosphates
- Organophosphorus Compounds/toxicity
- Zebrafish
- PubMed
- 33454525 Full text @ J. Hazard. Mater.
Citation
Shi, Q., Guo, W., Shen, Q., Han, J., Lei, L., Chen, L., Yang, L., Feng, C., Zhou, B. (2020) In vitro biolayer interferometry analysis of acetylcholinesterase as a potential target of aryl-organophosphorus flame-retardants. Journal of hazardous materials. 409:124999.
Abstract
Organophosphorus flame retardants (OPFRs) have been implicated as neurotoxicants, but their potential neurotoxicity and mechanisms remain poorly understood. Herein, we investigated the neurotoxicity of selected OPFRs using zebrafish as a model organism. Environmentally relevant concentrations (3-1500 nM) of three classes of OPFRs (aryl-OPFRs, chlorinated-OPFRs, and alkyl-OPFRs) were tested in zebrafish larvae (2-144 h post-fertilisation) alongside the neurotoxic chemical chlorpyrifos (CPF) that inhibits acetylcholinesterase (AChE). Exposure to aryl-OPFRs and CPF inhibited AChE activities, while chlorinated- and alkyl-OPFRs did not inhibit these enzymes. Biolayer interferometry (BLI) was used to probe interactions between OPFRs and AChE. The association and dissociation response curves showed that, like CPF, all three selected aryl-OPFRs, triphenyl phosphate (TPHP), tricresyl phosphate (TCP) and cresyl diphenyl phosphate (CDP), bound directly to AChE. The affinity constant (KD) for TPHP, TCP, CDP and CPF was 2.18 × 10-4, 5.47 × 10-5, 1.05 × 10-4 and 1.70 × 10-5 M, respectively. In addition, molecular docking revealed that TPHP, TCP, CDP and CPF bound to AChE with glide scores of - 7.8, - 8.3, - 8.1 and - 7.3, respectively. Furthermore, the calculated binding affinity between OPFRs and AChE correlated well with the KD values measured by BLI. The present study revealed that aryl-OPFRs can act as potent AChE inhibitors, and may therefore present a significant ecological risk to aquatic organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping