Physiological significance of the novel ability of microcystin LR from blue-green algae to induce epithelial-mesenchymal transition
| Project/Area Number |
19K06222
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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 40040:Aquatic life science-related
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| Research Institution | Kagoshima University |
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Principal Investigator |
Komatsu Masaharu 鹿児島大学, 農水産獣医学域水産学系, 教授 (30325815)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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 | Microcystin-LR / Acteoside / 上皮・間葉転換 / OATP1B3 / 生薬イワジシャ / microcystin-LR / アノイキス抵抗性 / 間葉・上皮転換 / リン酸化 / p53 / AKT / マイクロシスチン / OATP / 上皮間葉転換 / 細胞毒性 |
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| Outline of Research at the Start |
肝臓毒マイクロシスチンLR (MC-LR)は、高濃度曝露により肝細胞毒性を発揮し肝機能不全を引き起こす。一方、低濃度の慢性曝露により肝細胞増殖活性を発揮し、何かしらの要因でDNAにダメージを受けた肝細胞に対して肝がんの発がんプロモーターとして機能する。研究代表者らは、MC-LR曝露後の一部の細胞が剥離・浮遊するにもかかわらず、死滅から逃れ数日後には再生する新奇な現象を発見した。そこで、このアノイキス抵抗性細胞への形質転換誘導能の発現に関する分子機序の詳細を明らかにする。また、この新奇な形質転換に対して抑制的に働く化合物の探索にも検討を加える。
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| Outline of Final Research Achievements |
After exposure to microcystin-LR, detached and floating cells were collected and analyzed for changes in E-cadherin expression, which showed a marked decrease in expression of both genes and proteins. The cells that reattached after detachment and suspension were resistant to nodularin and okadaic acid as well as microcystin-LR, and after 3 months of passaging, microcystin-LR was not detected in the cells, indicating that the sensitivity to microcystin-LR is similar to that of parental cells.
In addition, Acteoside, a component of the crude drug Iwajisha, inhibited the cellular uptake of Microcystin-LR via OATP1B3 and attenuated its cytotoxicity.
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| Academic Significance and Societal Importance of the Research Achievements |
近い将来に水道法の改正等によりMicrocystin-LRが「要検討項目」から少なくとも「水質管理目標設定項目」に引き上げられることが望まれ、結果的に我が国の健康水準がより上昇することが期待される。さらにMicrocystin-LR、Nodularin、およびOkadaic acid中毒、ならびに疫学的因果関係が不明の肝臓障害の発生予防や対症療法の確立に貢献し、水圏生命科学領域における「食と健康」・「水と健康」研究を通じて世界中の人類の公衆衛生の向上に寄与することが期待される。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Enhancement of Edwardsiella piscicida infection, biofilm formation, and motility caused by N-acetylneuraminate lyase.2022
Author(s)
Vo, KL., Tran, TN., Kubo, Y., Sahashi, D., Komatsu, M., Shiozaki, K.
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Journal Title
Glycoconj. J.
Volume: -
Issue: 3
Pages: 429-442
DOI
Related Report
Peer Reviewed
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[Journal Article] The involvement of Nile tilapia (Oreochromis niloticus) Neu4 sialidase in neural differentiation during early ontogenesis.2021
Author(s)
Honda, A., Hayasaka, O., Mio, K., Fujimura, K., Kotani, T., Komatsu, M., Shiozaki, K.
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Journal Title
Biochimie
Volume: 185
Pages: 105-116
DOI
Related Report
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[Journal Article] Host lactosylceramide enhances Edwardsiella tarda infection.2021
Author(s)
Oishi, K., Morise, M., Vo, KL., Tran, TN., Sahashi, D., Ueda-Wakamatsu, R., Nishimura, W., Komatsu, M., Shiozaki, K.
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Journal Title
Cellular Microbiology
Volume: 23
Issue: 9
DOI
Related Report
Peer Reviewed
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