Evidence map›Paper›PMID 24349255›Full record

ArticlePloS one2013

Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced apoptosis.

Yuko Akazawa, Hajime Isomoto, Kayoko Matsushima, Tsutomu Kanda, Hitomi Minami, Naoyuki Yamaghchi, Naota Taura, Ken Shiozawa, Ken Ohnita, Fuminao Takeshima and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

50 citing papers in PubMed, 82 citations in OpenAlex.

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  10. Strategies ofFrontiers in cellular and infection microbiology · 2024
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  12. International journal of molecular sciences · 2023
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  15. Article
  16. Helicobacter pylori and gastric cancer: a lysosomal protease perspective.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022
    Review
  17. Review
  18. Article
  19. Fermented kimchi rejuvenated precancerous atrophic gastritis via mitigatingJournal of clinical biochemistry and nutrition · 2021
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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

14 authors at 3 institutions in 2 countries.

Yuko AkazawaDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Hajime IsomotoDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Kayoko MatsushimaDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Tsutomu KandaDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Hitomi MinamiDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Naoyuki YamaghchiDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Naota TauraDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Ken ShiozawaDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Ken OhnitaDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Fuminao TakeshimaDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Masayuki NakanoDepartment of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Joel MossCardiovascular and Pulmonary Branch, NHLBI, National Institutes of Health, Bethesda, Maryland, United States of America.
Toshiya HirayamaDepartment of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Kazuhiko NakaoDepartment of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan.
Nagasaki University Hospital · JPNagasaki University · JPNational Heart Lung and Blood Institute · US

Funding

ADP-ribosylation CyclesZIAHL000659 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MOSS, JOEL · 2009 to 2025
$29.8M
6 · The paper itself

Abstract

Vacuolating cytotoxin A (VacA) is one of the important virulence factors produced by H. pylori. VacA induces apoptotic cell death, which is potentiated by ammonia. VacA also causes cell death by mitochondrial damage, via signaling pathways that are not fully defined. Our aim was to determine whether endoplasmic reticulum (ER) stress is associated with VacA-induced mitochondrial dysfunction and apoptosis. We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. The effect of VacA on CHOP induction was significantly enhanced by co-incubation with ammonium chloride. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Knockdown of CHOP by siRNA resulted in inhibition of VacA-induced apoptosis. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. Activation of ER stress and up-regulation of BH3-only proteins were also observed in human H. pylori-infected gastric mucosa. Collectively, this study reveals a possible association between VacA-induced apoptosis in gastric epithelial cells, and activation of ER stress in H. pylori-positive gastric mucosa.

Indexed as

ApoptosisEndoplasmic Reticulum StressAmmonium ChlorideApoptosis Regulatory ProteinsBacterial ProteinsBcl-2-Like Protein 11BiomarkersCell Line, TumoreIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEukaryotic Initiation Factor-2Gastric MucosaGene Expression RegulationHeat-Shock ProteinsHelicobacter pyloriHumansAmmonium ChlorideApoptosis Regulatory ProteinsBacterial ProteinsBCL2L11 protein, humanBcl-2-Like Protein 11BiomarkerseIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEukaryotic Initiation Factor-2Heat-Shock ProteinsMembrane ProteinsProto-Oncogene ProteinsRNA, MessengerTranscription Factor CHOPVacA protein, Helicobacter pylori

Identifiers

PMID24349255
PMCPMC3862672
OpenAlexW2117655685

What OpenQuestion holds

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LicenceCC0
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Registered trials

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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.