2021 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
細菌学
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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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