Functional analysis of exosome siRNA in Cholix-induced hepatic cell death
| Project/Area Number |
19K07534
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49050:Bacteriology-related
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| Research Institution | Kyoto Pharmaceutical University (2021)
Chiba University (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 細菌毒素 / ADP-リボシル化 / PHB / マイクロアレイ解析 / miRNA / エキソソーム / 細胞死 / ADP-リボシル化毒素 / マイクロアレイ / Cholix / マイクロRNA |
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| Outline of Research at the Start |
コレラ菌由来外毒素 Cholix toxin (Cholix) は、宿主細胞内に侵入後、eEF2 を ADP-リボシル化し、タンパク質合成阻害活性に起因するアポトーシスを引き起こす蛋白質毒素である。本研究は、ヒト由来不死化正常肝細胞を用い、細胞致死に至る過程で放出されるエキソソーム内の microRNA (miRNA) を解析し、新たな細胞死亢進因子、致死過程特異的なコミュニケーション因子の同定・機能解析を行うことを目的とする。
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| Outline of Final Research Achievements |
Cholix cytotoxin (Cholix) was identified as a novel eukaryotic elongation factor 2 (eEF2) ADP-ribosyltransferase produced mainly in non-O1/non-O139 V. cholerae. The function and role of Cholix in infectious disease caused by V. cholerae remain unknown. we identified prohibitin (PHB) 1 and 2 as novel Cholix-interacting membrane proteins in immortalized human hepatocytes.Cholix-induced reactive oxygen species (ROS) production and accumulation of fragmented mitochondria were enhanced in PHB-knockdown cells.Our findings identify PHB as a new protein that interacts with Cholix and is involved in Cholix-induced mitochondrial dysfunction and cytoskeletal rearrangement by ROCK1 activation during apoptosis. In addition, we investigated the change of mRNA or miRNA by RNAseq or miRNA microarray analysis in Cholix-treated cells. We believed that these data are crucial informations to provide us novel cell damage or response pathways.
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| Academic Significance and Societal Importance of the Research Achievements |
緑膿菌の産生するExoA とよく似た構造と活性を持つ Cholix は、肝障害を引き起こす毒素である。 今回、Cholix の新規宿主細胞由来結合蛋白質としてProhibitin1,2 (PHB) を同定した。Cholix の細胞死に PHB が関与している事が分かった。ヒト由来不死化正常肝臓細胞を用いて Cholix による細胞内の mRNA, miRNA の網羅的解析（RNAseq 解析、マイクロアレイ解析）を行った。この解析結果は、これまで未知であった ADP-リボシル化による細胞死において、新規の宿主障害機構を見い出す貴重な基礎データとなると確信している。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival.2020
Author(s)
Yahiro, K., Ogura, K., Goto, Y., Iyoda, S., Kobayashi, T., Takeuchi, H., Ohnishi, M., Moss, J.
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Journal Title
Scientific Reports.
Volume: 10
Issue: 1
Pages: 18943-18943
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice2019
Author(s)
Suzuki H, Ataka K, Asakawa A, Cheng KC, Ushikai M, Iwai H, Yagi T, Arai T, Yahiro K, Yamamoto K, Yokoyama Y, Kojima M, Yada T, Hirayama T, Nakamura N, Inui A
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 6011-6011
DOI
Related Report
Peer Reviewed / Open Access
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