| Autor: |
Muñoz-Torrero D; Laboratory of Medicinal Chemistry (CSIC Associated Unit), Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, Barcelona 08028, Spain., Schopfer LM; University of Nebraska Medical Center, Omaha, Nebraska 68198, United States., Lockridge O; University of Nebraska Medical Center, Omaha, Nebraska 68198, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
Chemical research in toxicology [Chem Res Toxicol] 2023 Jan 16; Vol. 36 (1), pp. 112-121. Date of Electronic Publication: 2023 Jan 04. |
| DOI: |
10.1021/acs.chemrestox.2c00333 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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