Evidence map›Paper›PMID 20668524›Full record

ArticlePloS one2010

Role of the ATM-checkpoint kinase 2 pathway in CDT-mediated apoptosis of gingival epithelial cells.

Mounia Alaoui-El-Azher, Jeffrey J Mans, Henry V Baker, Casey Chen, Ann Progulske-Fox, Richard J Lamont, Martin Handfield

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  4. The Cell-Cycle Regulatory Protein p21Pathogens (Basel, Switzerland) · 2020
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  5. Virulence and Pathogenicity Properties ofPathogens (Basel, Switzerland) · 2019
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  8. Article
  9. Subversion of host genome integrity by bacterial pathogens.Nature reviews. Molecular cell biology · 2016
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
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

7 authors at 2 institutions in 1 country.

Mounia Alaoui-El-AzherDepartment of Oral Biology and Center for Molecular Microbiology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America.
Jeffrey J Mans
Henry V Baker
Casey Chen
Ann Progulske-Fox
Richard J Lamont
Martin Handfield
University of Florida · USUniversity of Southern California · US

Funding

P GINGIVALIS INTERACTIONS WITH GINGIVAL EPITHELIAL CELLSR01DE011111 · NIDCR · UNIVERSITY OF WASHINGTON · PI HARIBABU BODDULURI, Richard J Lamont · 1995 to 2026
$5.4M
P.gingivalis Interactions with Gingival Epithelial CellsR37DE011111 · NIDCR · UNIVERSITY OF LOUISVILLE · PI LAMONT, RICHARD J · 2009 to 2018
$3.6M
Epithelium-Microbe Interactions Dissected with ArraysR01DE016715 · NIDCR · UNIVERSITY OF FLORIDA · PI PROGULSKE-FOX, ANN · 2006 to 2010
$1.4M
NIDCR NIH HHS DE11111NIDCR NIH HHS DE16715NIDCR NIH HHS R01 DE011111NIDCR NIH HHS R01 DE016715NIDCR NIH HHS R37 DE011111
6 · The paper itself

Abstract

The cytolethal distending toxin (CDT) of the oral pathogen Aggregatibacter actinomycetemcomitans induces cell cycle arrest and apoptosis in various cell types. Western analysis, pharmacological inhibition and siRNA silencing were performed in human immortalized gingival keratinocytes (HIGK) to dissect the functional role of the ataxia telangiectasia mutated (ATM) pathway in the signal transduction steps triggered by the CDT. Infection of HIGK was associated with a time-dependent induction of cytoplasmic histone-associated DNA fragmentation. However, in the absence of CDT, infected HIGK underwent reversible DNA strand breaks but not apoptosis, while caspase 3 activity, p21 levels, and HIGK viability were unaffected. Caspase 9 activity was attenuated in the CDT mutant-infected HIGK compared to wild-type infected cells. Pharmacological inhibition and siRNA-silencing of the ATM downstream effector, the protein kinase checkpoint kinase 2 (Chk2), significantly impacted CDT-mediated apoptosis. Together, these findings provide insight on the specificity of the ATM-Chk2 pathway in response to the CDT of A. actinomycetemcomitans in oral epithelial cells, which ultimately leads to apoptosis. We further propose the existence of an unidentified factor that is distinct from the CDT, and involved with a reversible DNA fragmentation that does not trigger terminal apoptosis in oral epithelial cells. This model potentially explains conflicting reports on the biological activity of the A. actinomycetemcomitans CDT.

Indexed as

Aggregatibacter actinomycetemcomitansApoptosisAtaxia Telangiectasia Mutated ProteinsBacterial ToxinsBlotting, WesternCaspase 3Caspase 9Cell Cycle ProteinsCell LineCheckpoint Kinase 2Cyclin-Dependent Kinase Inhibitor p21DNA-Binding ProteinsDNA Breaks, Double-StrandedEpithelial CellsGingivaHumansAtaxia Telangiectasia Mutated ProteinsATM protein, humanBacterial ToxinsCaspase 3Caspase 9CDKN1A protein, humanCell Cycle ProteinsCheckpoint Kinase 2CHEK2 protein, humanCyclin-Dependent Kinase Inhibitor p21cytolethal distending toxinDNA-Binding ProteinsProtein Serine-Threonine KinasesRNA, Small InterferingTumor Suppressor Proteins

Identifiers

PMID20668524
PMCPMC2909199
OpenAlexW1989930451

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.