Study on the Biomolecular Competitive Mechanism of Polybrominated Diphenyl Ethers and Their Derivatives on Thyroid Hormones.
Molecules
; 28(21)2023 Oct 31.
Article
en En
| MEDLINE
| ID: mdl-37959791
ABSTRACT
Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants. PBDEs and their derivatives, hydroxylated PBDEs (OH-PBDEs), can bind to hormone receptors and impact hormone secretion, transportation, and metabolism, leading to endocrine disruption and the development of various diseases. They have particularly strong interference effects on thyroid hormones. This study used decabromodiphenyl ether (BDE-209); 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); and 6-OH-BDE-47 as representative compounds of PBDEs and their derivatives, OH-PBDEs. A fluorescence probe, fluorescein-isothiocyanate-L-thyroxine (FITC-T4, F-T4), specific for binding to transthyretin (TTR), a thyroid transport protein, was prepared. The binding capacity of PBDEs and their derivatives, OH-PBDEs, to TTR was quantitatively measured using fluorescence spectroscopy. The principle of quenching the fluorescence intensity of F-T4 after binding to TTR was used to analyze the competitive interaction between the probe and BDE-209, BDE-47, and 6-OH-BDE-47, thereby evaluating the toxic effects of PBDEs and their derivatives on the thyroid system. Additionally, AutoDock molecular docking software (1.5.6) was used to further analyze the interference mechanism of OH-PBDEs on T4. The results of the study are as follows (1) Different types of PBDEs and OH-PBDEs exhibit varying degrees of interference with T4. Both the degree of bromination and hydroxylation affect their ability to competitively bind to TTR. Higher bromination and hydroxylation degrees result in stronger competitive substitution. (2) The competitive substitution ability of the same disruptor varies at different concentrations. Higher concentrations lead to stronger substitution ability, but there is a threshold beyond which the substitution ability no longer increases. (3) When OH-PBDEs have four or more bromine atoms and exhibit the most structural similarity to T4, their binding affinity to TTR is stronger than that of T4.
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Banco de datos:
MEDLINE
Asunto principal:
Hormonas Tiroideas
/
Éteres Difenilos Halogenados
Idioma:
En
Año:
2023
Tipo del documento:
Article