Chlorpyrifos oxon activates glutamate and lysine for protein cross-linking
| Autor: | Diego Muñoz-Torrero, Lawrence M. Schopfer, Oksana Lockridge |
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| Přispěvatelé: | National Institutes of Health (US), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Popis: | Chronic 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. This work was supported in part by the Fred & Pamela Buffet Cancer Center Support Grant [grant number P30CA036727] from the National Institutes of Health and by Ministerio de Ciencia e Innovacioń and Agencia Estatal de Investigacioń MCIN/AEI/10.13039/501100011033 [grant number PID2020-118127RB-I00]. |
| Databáze: | OpenAIRE |
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