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Molecular basis for onset of the novel 3rd toxicity of cyanotoxin microcystin-LR

Research Project

Project/Area Number 16K07875
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Aquatic life science
Research InstitutionKagoshima University

Principal Investigator

Komatsu Masaharu  鹿児島大学, 農水産獣医学域水産学系, 教授 (30325815)

Research Collaborator Takumi Shota  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsマイクロシスチン / OATP1B3 / アノイキス抵抗性 / 上皮・間葉転換 / 間葉・上皮転換 / マイクロシスチンLR / ノジュラリン / OATP1B1 / ファロイジン / 生薬 / アクテオシド / ハイポキシア / アノイキス / 毒性学 / 生理活性 / 衛生 / シグナル伝達 / 水産学
Outline of Final Research Achievements

HEK293-OATP1B3FL (FL cells) and HEK293-OATP1B3AD (AD cells), which were transfomed cells after the parental HK293-OATP1B3 cells were exposed to MC-LR, were resistant to hypoxia than their parental cells.
Attenuation activity to the MC-LR cytotoxicity was detected in herbal medicines Iwajisha and Kin-oshi. In addition, we found that their components, acteoside, quercetin, and kaempferol were the active substances.

Academic Significance and Societal Importance of the Research Achievements

アオコに由来する肝臓毒マイクロシスチンLRは,高濃度で肝機能不全を誘発し,低濃度慢性曝露により肝臓がんの発がん物質として作用する。本研究により,マイクロシスチンLRに肝がんの浸潤・転移を誘発する可能性があることを実験室レベルで示した。また,マイクロシスチンLRの細胞毒性を抑制する化合物を生薬中に見出した。発見した物質は野菜や果物にも含まれる成分であり,生薬や食事によりマイクロシスチンLR中毒を予防でき,また,発がんおよびがんの転移を抑える可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (13 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] ドイツがん研究センター(ドイツ)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Ubiquitous distribution of fluorescent protein in muscles of four species and two subspecies of eel (genus Anguilla).2017

    • Author(s)
      Aki Funahashi, Takao Itakura, Abeer A.I. Hassanin, Masaharu Komatsu, Seiichi Hayashi, Yoshio Kaminishi
    • Journal Title

      Journal of Genetics

      Volume: 96 Issue: 1 Pages: 127-133

    • DOI

      10.1007/s12041-017-0751-5

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Overexpression of Carboxylesterase Contributes to the Attenuation of Cyanotoxin Microcystin-LR Toxicity2017

    • Author(s)
      Shota Takumi, Tai Shimono, Satoshi Ikema, Yuki Hotta, Petros Kingstone Chigwechokha, Kazuhiro Shiozaki, Yasumasa Sugiyama, Mitsuru Hashimoto, Tatsuhiko Furukawa, Masaharu Komatsu
    • Journal Title

      Comparative Biochemistry and Phyisiology part-C

      Volume: 194 Pages: 22-27

    • DOI

      10.1016/j.cbpc.2017.01.008

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Suppression of Neu1 sialidase delays the absorption of yolk sac in medaka (Oryzias latipes) accompanied with the accumulation of alpha 2-3 sialo-glycoproteins.2017

    • Author(s)
      Sena Ryuzono, Ryo Takase, Yuko Kamada, Takanori Ikenaga, Petros Kingstone Chigwechokha, Masaharu Komatsu, Kazuhiro Shiozaki
    • Journal Title

      Biochmie

      Volume: 135 Pages: 63-71

    • DOI

      10.1016/j.biochi.2017.01.008

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Matrix metalloproteinase-7 inhibitory activity of lipid extract from dwarf gulper shark (Centrophorus atromarginatus) through down-regulation of gene transcription.2017

    • Author(s)
      Kazuhiro Shiozaki, Minori Yoshikawa, Saori Kiguchiya, Asami Ikeda, Yuko Kamada, Petros Kingstone Chigwechokha and Masaharu Komatsu
    • Journal Title

      Journal of Functional Foods

      Volume: 30 Pages: 90-96

    • DOI

      10.1016/j.jff.2017.01.013

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Naringenin suppresses Edwardsiella tarda infection in GAKS cells by NanA sialidase inhibition2017

    • Author(s)
      Shinyoshi S., Y. Kamada, K. Matsusaki, P.K. Chigwechokha, S. Tepparin, K. Araki, M. Komatsu, K. Shiozaki
    • Journal Title

      Fish Shellfish Immunol.

      Volume: 61 Pages: 86-92

    • DOI

      10.1016/j.fsi.2016.12.018

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation.2016

    • Author(s)
      Ayana Yoshinaga, Natsuki Kajiya, Kazuki Oishi, Yuko Kamada, Asami Ikeda, Petros Kingstone Chigwechokha, Toshiro Kibe, Michiko Kishida, Shosei Kishida, Masaharu Komatsu, Kazuhiro Shiozaki
    • Journal Title

      European Journal of Pharmacology

      Volume: 782 Pages: 21-29

    • DOI

      10.1016/j.ejphar.2016.04.035

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive regulation of myoblast differentiation by medaka Neu3b sialidase through ganglioside desialylation2016

    • Author(s)
      Shiozaki, K., Harasaki, Y., Fukuda, M., Yoshinaga, A., Ryuzono, S., Chigwechokha, P., Komatsu M., Miyagi, T.
    • Journal Title

      Biochimie

      Volume: 123 Pages: 65-72

    • DOI

      10.1016/j.biochi.2016.01.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Eel green fluorescent protein is associated with resistance to oxidative stress.2016

    • Author(s)
      Aki Funahashi, Masaharu Komatsu, Tatsuhiko Furukawa, Yuki Yoshizono, Hikari Yoshizono, Yasuhiro Orikawa, Shota Takumi, Kazuhiro Shiozaki, Seiichi Hayashi, Yoshio Kaminishi, Takao Itakura.
    • Journal Title

      Comparative Biochemistry and Physiology-part C

      Volume: 181-182 Pages: 35-39

    • DOI

      10.1016/j.cbpc.2015.12.009

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lysosomal localization of Japanese medaka (Oryzias latipes) Neu1 sialidase and its highly conserved enzymatic profiles with human.2016

    • Author(s)
      Ryuzono, S., Takase, R., Oishi, K., Ikeda, A., Chigwechokha, P., Funahashi, A., Komatsu, M., Miyagi, T., Shiozaki, K.,
    • Journal Title

      Gene

      Volume: 575 Issue: 2 Pages: 513-523

    • DOI

      10.1016/j.gene.2015.09.028

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ATP7B expression confers multidrug resistance through drug sequestration2015

    • Author(s)
      Moinuddin FM, Shinsato Y, Komatsu M, Mitsuo R, Minami K, Yamamoto M, Kawahara K, Hirano H, Arita K, Furukawa T
    • Journal Title

      Oncotarget

      Volume: NA Issue: 16 Pages: 22779-22790

    • DOI

      10.18632/oncotarget.8059

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] OATP1B3発現細胞にmicrocystin-LRおよびnodularinを曝露することにより誘導される上皮間葉転換様の形質転換細胞の性状解析2018

    • Author(s)
      富岡 優、何 偉傑、塩崎一弘、古川龍彦、内匠正太、小松正治
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ケルセチンを用いた肝臓毒マイクロシスチンLRの細胞毒性の抑制2018

    • Author(s)
      何 偉傑、富岡 優、塩崎一弘、古川龍彦、内匠正太、小松正治
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒゲナガエビ頭部の有効利用と機能性2017

    • Author(s)
      杉山 靖正,久木野 千波,福山 智未,吉岡 涼代,山田 章二,小松 正治
    • Organizer
      日本農芸化学会
    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Presentation] NodularinはOATP1B3発現細胞に対して上皮間葉転換様の形質転換を誘導する2017

    • Author(s)
      富岡 優、内匠 正太、杉山靖正、塩崎一弘、古川龍彦、小松正治
    • Organizer
      生命化学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 魚類肝臓細胞におけるガングリオシド脱シアリル化を介した脂質蓄積制御機構の解明2017

    • Author(s)
      大石一樹、宮﨑未奈、髙瀬 諒、西村 渉、小松正治、塩﨑一弘
    • Organizer
      生命化学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] Edwardsiella tardaの病原性を制御するNanAシアリダーゼ2017

    • Author(s)
      都築利治、二神裕子、Vo Khanh Linh、Irandha CM Siahaan、小松正治、塩﨑一弘
    • Organizer
      平成29年度日本水産学会九州支部会
    • Related Report
      2017 Research-status Report
  • [Presentation] シアリドーシスモデルとしてのneu1ノックアウトゼブラフィッシュの作製2017

    • Author(s)
      高瀬 諒、前田悠太郎、小松正治、塩崎一弘
    • Organizer
      平成29年度日本水産学会九州支部会
    • Related Report
      2017 Research-status Report
  • [Presentation] アクテオシドを用いたマイクロシスチンLRおよびファロイジンの細胞毒性の抑制.2016

    • Author(s)
      橋本 海理,青木 俊二,池田 龍二,堀田 夕貴,塩崎 一弘,古川 龍彦,内匠 正太,小松 正治
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 肥満の発症におよぼすガングリオシド脱シアリル化の意義2016

    • Author(s)
      大石一樹,宮崎未奈,小松正治,塩﨑一弘
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 脊椎動物モデルへの応用を目指した魚類オートファジー・リソソーム分解系における脱シアリル化機構の解明2016

    • Author(s)
      高瀬 諒,本田晃伸,小松正治,塩﨑一弘
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] マイクロシスチンLRが誘導するアノイキス抵抗性細胞の低酸素応答2016

    • Author(s)
      堀田 夕貴,内匠 正太,橋本 海理,塩崎 一弘,池田 龍二,古川 龍彦,小松 正治
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒ素がコレステロール代謝に及ぼす影響2016

    • Author(s)
      内匠正太,小松正治,柳澤裕之
    • Organizer
      日本衛生学会
    • Place of Presentation
      旭川市民文化会館(北海道・旭川市)
    • Year and Date
      2016-05-11
    • Related Report
      2016 Research-status Report
  • [Presentation] 水生生物の効用と遺伝子及び生活環境2016

    • Author(s)
      小松正治
    • Organizer
      かごしま県民大学連携講座「からだの健康を遺伝子と生活環境から考える」
    • Place of Presentation
      かごしま県民交流センター(鹿児島県・鹿児島市)
    • Related Report
      2016 Research-status Report
  • [Book] 食の安全における安全な水 鹿児島大学重点領域研究「食と健康」, 鹿児島の食環境と健康食材2016

    • Author(s)
      小松正治
    • Publisher
      南方新社
    • Related Report
      2016 Research-status Report
  • [Remarks] 鹿児島大学水産学部 食品生命科学分野 小松・内匠研究室(ケミカルバイオロジー)

    • URL

      https://marinechemicalbiology.jimdo.com/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 鹿児島大学水産学部 食品生命科学分野 小松研究室

    • URL

      https://marinechemicalbiology.jimdo.com/

    • Related Report
      2017 Research-status Report 2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-07-01  

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