Muñoz-Torrero López-Ibarra, DiegoSchopfer, Lawrence M.Lockridge, Oksana2023-02-222023-02-2220230893-228Xhttps://hdl.handle.net/2445/193966Chronic low-dose exposure to organophosphorus (OP) toxicants is correlated with an increase in the risk of impaired cognition and neurodegenerative diseases. A mechanism to explain this relationship is needed. We suggest that the formation of organophosphate-induced high-molecular-weight protein aggregates that disrupt cell function may be the missing link. It has been demonstrated that such aggregation can be promoted by OP-labeled lysine. Alternatively, OP-labeled glutamate may be the initiator. To test this hypothesis, we treated MAP-rich tubulin Sus scrofa and human transglutaminase with chlorpyrifos oxon. Trypsin-digested proteins were subjected to liquid chromatography−tandem mass spectrometry followed by Protein Prospector searches to identify diethyl phosphate adducts and cross-linked peptides. We report the presence of diethyl phosphate adducts on the side chains of glutamate, lysine, and tyrosine, as well as cross-links between glutamate and lysine. Glutamate-lysine cross-linking could be initiated either by diethyl phosphate-activated glutamate or by diethyl phosphate-activated lysine to form stable isopeptide bonds between and within proteins. It was concluded that organophosphate-induced high-molecular-weight protein aggregates could promote brain dysfunction.10 p.application/pdfengcc by-nc-nd (c) Diego Muñoz-Torrero López-Ibarra, et al., 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/Malalties neurodegenerativesPèptidsProteïnesÀcids nucleicsNeurodegenerative DiseasesPeptidesProteinsNucleic acidsinfo:eu-repo/semantics/article7283582023-02-22info:eu-repo/semantics/openAccess