Evidence map›Paper›PMID 19631231›Full record

ArticleToxicology and applied pharmacology2009

Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon: implications for neurotoxicity.

Hasmik Grigoryan, Oksana Lockridge

Open access · greenAbstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Risk Factors for Brain Health in Agricultural Work: A Systematic Review.International journal of environmental research and public health · 2022
    Pooled it
  2. Review
  3. Is Gulf War Illness a prolonged early phase tauopathy?Cytoskeleton (Hoboken, N.J.) · 2024
    Article
  4. Retinal Toxicity Induced by Chemical Agents.International journal of molecular sciences · 2022
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. AnToxicology research · 2016
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos.Toxicological sciences : an official journal of the Society of Toxicology · 2010
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Hasmik GrigoryanUniversity of Nebraska Medical Center, Eppley Institute for Cancer Research, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Oksana Lockridge
University of Nebraska Medical Center · US

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Apar Kishor Ganti · 1985 to 2026
$55.0M
Mass Spectrometry in Clinical Diagnosis of Nerve Agent ExposureU01NS058056 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI LOCKRIDGE, OKSANA · 2006 to 2008
$1.4M
NCI NIH HHS P30 CA036727NCI NIH HHS P30CA36727NINDS NIH HHS U01 NS058056
6 · The paper itself

Abstract

Organophosphorus agents cause cognitive deficits and depression in some people. We hypothesize that the mechanism by which organophosphorus agents cause these disorders is by modification of proteins in the brain. One such protein could be tubulin. Tubulin polymerizes to make the microtubules that transport cell components to nerve axons. The goal of the present work was to measure the effect of the organophosphorus agent chlorpyrifos oxon on tubulin polymerization. An additional goal was to identify the amino acids covalently modified by chlorpyrifos oxon in microtubule polymers and to compare them to the amino acids modified in unpolymerized tubulin dimers. Purified bovine tubulin (0.1 mM) was treated with 0.005-0.1 mM chlorpyrifos oxon for 30 min at room temperature and then polymerized by addition of 1 mM GTP to generate microtubules. Microtubules were visualized by atomic force microscopy. Chlorpyrifos oxon-modified residues were identified by tandem ion trap electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry of tryptic peptides. Nanoimaging showed that low concentrations (0.005 and 0.01 mM) of chlorpyrifos oxon yielded short, thin microtubules. A concentration of 0.025 mM stimulated polymerization, while high concentrations (0.05 and 0.1 mM) caused aggregation. Of the 17 tyrosines covalently modified by chlorpyrifos oxon in unpolymerized tubulin dimers, only 2 tyrosines were labeled in polymerized microtubules. The two labeled tyrosines in polymerized tubulin were Tyr 103 in EDAANNYR of alpha tubulin, and Tyr 281 in GSQQYR of beta tubulin. In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents.

Indexed as

NanostructuresAnimalsCattleChlorpyrifosCholinesterase InhibitorsDose-Response Relationship, DrugGuanosine TriphosphateMicroscopy, Atomic ForceNeurotoxicity SyndromesProtein MultimerizationSpectrometry, Mass, Electrospray IonizationSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationTandem Mass SpectrometryTubulinTubulin ModulatorsTyrosineChlorpyrifosCholinesterase InhibitorsGuanosine TriphosphateO,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphateTubulinTubulin ModulatorsTyrosine

Identifiers

PMID19631231
PMCPMC2753691
OpenAlexW2008352893

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.