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2023

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cc by-nc-nd (c) Diego Muñoz-Torrero López-Ibarra, et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/193966

Chlorpyrifos oxon activates glutamate and lysine for protein cross-linking

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Recurs relacionat

https://doi.org/10.1021/acs.chemrestox.2c00333

Resum

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.

Matèries

Malalties neurodegeneratives, Pèptids, Proteïnes, Àcids nucleics

Matèries (anglès)

Neurodegenerative Diseases, Peptides, Proteins, Nucleic acids

Citació

Col·leccions

Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

Citació

MUÑOZ-TORRERO LÓPEZ-IBARRA, Diego, SCHOPFER, Lawrence M. and LOCKRIDGE, Oksana. Chlorpyrifos oxon activates glutamate and lysine for protein cross-linking. Chemical Research in Toxicology. 2023. Vol. 36, num. 1, pags. 112-121. ISSN 0893-228X. [consulted: 19 of August of 2026]. Available at: https://hdl.handle.net/2445/193966

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