ArticleThe Journal of biological chemistry2018
Chlorpyrifos oxon promotes tubulin aggregation via isopeptide cross-linking between diethoxyphospho-Lys and Glu or Asp: Implications for neurotoxicity.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Stable Protein-Based G-Quadruplex-Derived Supramolecular Bioinks as Tunable ECM-Mimetic Constructs Assembled by Combining Non-Covalent and Covalent Strategies.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Chlorpyrifos and Chlorpyrifos-Oxon: A Widening Spectrum of Toxicity.International journal of molecular sciences · 2026Review
- Review: Organophosphorus toxicants, in addition to inhibiting acetylcholinesterase activity, make covalent adducts on multiple proteins and promote protein crosslinking into high molecular weight aggregates.Chemico-biological interactions · 2023Review
- Chlorpyrifos Oxon Activates Glutamate and Lysine for Protein Cross-linking.Chemical research in toxicology · 2023Article
- Dichlorvos-induced formation of isopeptide crosslinks between proteins in SH-SY5Y cells.Analytical biochemistry · 2022Article
- Organophosphorus Pesticides Promote Protein Cross-Linking.Chemical research in toxicology · 2022Article
- Rabbit Antidiethoxyphosphotyrosine Antibody, Made by Single B Cell Cloning, Detects Chlorpyrifos Oxon-Modified Proteins in Cultured Cells and Immunopurifies Modified Peptides for Mass Spectrometry.Journal of proteome research · 2021Article
- Bbc3 Loss Enhances Survival and Protein Clearance in Neurons Exposed to the Organophosphate Pesticide Chlorpyrifos.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Evaluation of mass spectrometry MS/MS spectra for the presence of isopeptide crosslinked peptides.PloS one · 2021Article
- Characteristic fragment ions associated with dansyl cadaverine and biotin cadaverine adducts on glutamine.Analytical biochemistry · 2020Article
- Article
- Chlorpyrifos Oxon-Induced Isopeptide Bond Formation in Human Butyrylcholinesterase.Molecules (Basel, Switzerland) · 2020Article
- Neuropathy target esterase (NTE/PNPLA6) and organophosphorus compound-induced delayed neurotoxicity (OPIDN).Advances in neurotoxicology · 2020Article
- Article
- Half-life of chlorpyrifos oxon and other organophosphorus esters in aqueous solution.Chemico-biological interactions · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Exposure to organophosphorus toxicants (OP) can have chronic adverse effects that are not explained by inhibition of acetylcholinesterase, the cause of acute OP toxicity. We therefore hypothesized that OP-induced chronic illness is initiated by the formation of organophosphorus adducts on lysine residues in proteins, followed by protein cross-linking and aggregation. Here, Western blots revealed that exposure to the OP chlorpyrifos oxon converted porcine tubulin from its original 55-kDa mass to high-molecular-weight aggregates. Liquid chromatography-tandem MS analysis of trypsin-digested samples identified several diethoxyphospho-lysine residues in the OP-treated tubulin. Using a search approach based on the Batch Tag program, we identified cross-linked peptides and found that these chemically activated lysines reacted with acidic amino acid residues creating γ-glutamyl-ϵ-lysine or aspartyl-ϵ-lysine isopeptide bonds between β- and α-tubulin. Of note, these cross-linked tubulin molecules accounted for the high-molecular-weight aggregates. To the best of our knowledge, this is the first report indicating that chlorpyrifos oxon-exposed tubulin protein forms intermolecular cross-links with other tubulin molecules, resulting in high-molecular-weight protein aggregates. It is tempting to speculate that chronic illness from OP exposure may be explained by a mechanism that starts with OP adduct formation on protein lysines followed by protein cross-linking. We further speculate that OP-modified or cross-linked tubulin can impair axonal transport, reduce neuron connections, and result in neurotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.