A high-affinity fluorescent probe for human uridine-disphosphate glucuronosyltransferase 1A9 function monitoring under environmental pollutant exposure.

Autor: Miao YS; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China., Wang JY; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China., Zhuang RR; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China., Huo XK; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China., Yi ZC; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China., Sun XN; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China; School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China., Yu ZL; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China., Tian XG; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China., Ning J; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China., Feng L; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; Chengdu University of Traditional Chinese Medicine, Chengdu 611137 China. Electronic address: leifeng@dmu.edu.cn., Ma XC; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address: maxc1978@163.com., Lv X; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China. Electronic address: lvxia19870630@163.com.
Jazyk: angličtina
Zdroj: Journal of hazardous materials [J Hazard Mater] 2024 Mar 05; Vol. 465, pp. 133439. Date of Electronic Publication: 2024 Jan 06.
DOI: 10.1016/j.jhazmat.2024.133439
Abstrakt: Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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