Covalent adduct formation of histone with organophosphorus pesticides in vitro.
Autor: | Chu S; Ecotoxicology and Wildlife Health Division, Wildlife and Landscape Science Directorate, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1A 0H3, Canada. Electronic address: Shaogang.chu@ec.gc.ca., Li XH; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian District, No. 18, Shuangqing Road, Beijing, 100085, PR China. Electronic address: lxhzpb@rcees.ac.cn., Letcher RJ; Ecotoxicology and Wildlife Health Division, Wildlife and Landscape Science Directorate, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1A 0H3, Canada. Electronic address: robert.letcher@ec.gc.ca. |
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Jazyk: | angličtina |
Zdroj: | Chemico-biological interactions [Chem Biol Interact] 2024 Aug 01; Vol. 398, pp. 111095. Date of Electronic Publication: 2024 Jun 04. |
DOI: | 10.1016/j.cbi.2024.111095 |
Abstrakt: | It is established that organophosphorus pesticide (OPP) toxicity results from modification of amino acids in active sites of target proteins. OPPs can also modify unrelated target proteins such as histones and such covalent histone modifications can alter DNA-binding properties and lead to aberrant gene expression. In the present study, we report on non-enzymatic covalent modifications of calf thymus histones adducted to selected OPPs and organophosphate flame retardants (OPFRs) in vitro using a bottom-up proteomics method approach. Histones were not found to form detectable adducts with the two tested OPFRs but were avidly modified by a few of the seven OPPs that were tested in vitro. Dimethyl phosphate (or diethyl phosphate) adducts were identified on Tyr, Lys and Ser residues. Most of the dialkyl phosphate adducts were identified on Tyr residues. Methyl and ethyl modified histones were also detected. Eleven amino residues in histones showed non-enzymatic covalent methylation by exposure of dichlorvos and malathion. Our bottom-up proteomics approach showing histone-OPP adduct formation warrants future studies on the underlying mechanism of chronic illness from exposure to OPPs. 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. (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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