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Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis
http://hdl.handle.net/10069/34190
http://hdl.handle.net/10069/34190bea243f4-04de-477b-8a96-4eac584efd01
名前 / ファイル | ライセンス | アクション |
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PLoS8_82322.pdf (1.3 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2014-03-11 | |||||
タイトル | ||||||
タイトル | Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Akazawa, Yuko
× Akazawa, Yuko× Isomoto, Hajime× Matsushima, Kayoko× Kanda, Tsutomu× Minami, Hitomi× Yamaghchi, Naoyuki× Taura, Naota× Shiozawa, Ken× Ohnita, Ken× Takeshima, Fuminao× Nakano, Masayuki× Moss, Joel× Hirayama, Toshiya× Nakao, Kazuhiko |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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 ERlocalized 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. | |||||
書誌情報 |
PLoS ONE 巻 8, 号 12, p. e82322, 発行日 2013-12-13 |
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出版者 | ||||||
出版者 | Public Library of Science | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 19326203 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0082322 | |||||
権利 | ||||||
権利情報 | This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PLoS ONE, 8(12), e82322; 2013 |