Evidence map›Paper›PMID 20561923›Full record

ArticleMicrobial pathogenesis2010

Subtilase cytotoxin induces apoptosis in HeLa cells by mitochondrial permeabilization via activation of Bax/Bak, independent of C/EBF-homologue protein (CHOP), Ire1alpha or JNK signaling.

Kinnosuke Yahiro, Naoko Morinaga, Joel Moss, Masatoshi Noda

Abstract read
In one paragraph

Article in Microbial pathogenesis, 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
1.5field-weighted citation impact, top 21% 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, 30 citations in OpenAlex.

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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

4 authors at 2 institutions in 2 countries.

Kinnosuke YahiroDepartment of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan. yahirok@faculty.chiba-u.jp
Naoko Morinaga
Joel Moss
Masatoshi Noda
Chiba University · JPNational Institutes of Health · US

Funding

Characterization of the Pathogenesis of Lymphangioleiomyomatosis (LAM)ZIAHL002541 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MOSS, JOEL · 2009 to 2025
$47.7M
ADP-ribosylation CyclesZIAHL000659 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MOSS, JOEL · 2009 to 2025
$29.8M
CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)Z01HL002541 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MOSS, JOEL · 1996 to 2008
$4.5M
Intramural NIH HHS Z01 HL002541Intramural NIH HHS ZIA HL000659Intramural NIH HHS ZIA HL002541
6 · The paper itself

Abstract

Subtilase cytotoxin (SubAB) is an AB(5) cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum (ER) chaperone, BiP, leading to transient inhibition of protein synthesis and cell cycle arrest at G(1) phase, and inducing caspase-dependent apoptosis via mitochondrial membrane damage in Vero cells. Here we investigated the mechanism of mitochondrial permeabilization in HeLa cells. SubAB-induced cytochrome c release into cytosol did not depend on mitochondrial permeability transition pore (PTP), since cyclosporine A did not suppress cytochrome c release. SubAB did not change the expression of anti-apoptotic Bcl-2 or Bcl-XL and pro-apoptotic Bax or Bak, but triggered Bax and Bak conformational changes and association of Bax with Bak. Silencing using siRNA of both bax and bak genes, but not bax, bak, or bim alone, resulted in reduction of cytochrome c release, caspase-3 activation, DNA ladder formation and cytotoxicity, indicating that Bax and Bak were involved in apoptosis. SubAB activated ER transmembrane transducers, Ire1alpha, and cJun N-terminal kinase (JNK), and induced C/EBF-homologue protein (CHOP). To investigate whether these signals were involved in cytochrome c release by Bax activation, we silenced ire1alpha, jnk or chop; however, silencing did not decrease SubAB-induced cytochrome c release, suggesting that these signals were not necessary for SubAB-induced mitochondrial permeabilization by Bax activation.

Indexed as

Apoptosisbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCaspase 3Cytochromes cCytoplasmEndoribonucleasesEscherichia coliEscherichia coli ProteinsGene SilencingHeLa CellsHumansMAP Kinase Kinase 4Mitochondrial MembranesPermeabilityProtein BindingBAK1 protein, humanBAX protein, humanbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCaspase 3Cytochromes cDDIT3 protein, humanEndoribonucleasesERN1 protein, humanEscherichia coli ProteinsMAP Kinase Kinase 4Protein Serine-Threonine KinasesRNA, Small Interferingsubtilase cytotoxin, E coliSubtilisinsTranscription Factor CHOP

Identifiers

PMID20561923
PMCPMC3417112
OpenAlexW1988270506

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.