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Elucidation of molecular mechanisms of bioprobes on signaling pathways of inflammatory responses and hypoxic responses

Research Project

Project/Area Number 16H04910
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied biochemistry
Research InstitutionKyoto Institute of Technology

Principal Investigator

KATAOKA Takao  京都工芸繊維大学, 応用生物学系, 教授 (20242307)

Co-Investigator(Kenkyū-buntansha) 木村 賢一  岩手大学, 農学部, 教授 (30344625)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords炎症性サイトカイン / 低酸素応答 / 情報伝達 / バイオプローブ / 糖鎖修飾 / NF-κB / HIF-1α / ICAM-1 / kujigamberol / 4-O-methylascochlorin / 4-hydroxypanduratin A / isopanduratin A / asiatic acid / シグナル伝達 / 生理活性 / 薬理学 / allantopyrone A / オイデスマン誘導体 / キナクリン / TNFレセプター1 / LTβ / RelA / RelB
Outline of Final Research Achievements

Pro-inflammatory cytokines induce the expression of genes, such as those encoding cell adhesion molecules and survival factors, via the activation of the transcription factor nuclear factor κB (NF-κB). In this study, the mechanisms of action of small molecules on NF-κB signaling pathway and gene expression were elucidated. Hypoxia-inducible factor-1α (HIF-1α) is the transcription factor essential for hypoxic responses. In this study, the mechanism of action of a small molecule on HIF-1α stabilization was elucidated.

Academic Significance and Societal Importance of the Research Achievements

本研究では、炎症性サイトカインのシグナル伝達や遺伝子発現を阻害する小分子化合物の作用メカニズム、並びに低酸素応答に重要な転写因子の安定化を誘導する作用メカニズムを解明した点で学術的意義がある。これらの研究成果は、炎症反応や低酸素応答の分子メカニズムの解明、及び汎用性の高いバイオプローブの開発に貢献することが期待される。さらに、社会的意義として、植物等の天然物由来の小分子化合物は、炎症性疾患、がん、虚血性疾患の予防薬・治療薬の開発に貢献することが期待される。

Report

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

    (29 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) Book (1 results)

  • [Int'l Joint Research] Vietnam National Univ., Ho Chi Minh City(ベトナム)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Catholic Univ. of Daegu School of Med.(韓国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 4-Hydroxypanduratin A and Isopanduratin A Inhibit Tumor Necrosis Factor α-Stimulated Gene Expression and the Nuclear Factor κB-Dependent Signaling Pathway in Human Lung Adenocarcinoma A549 Cells2019

    • Author(s)
      Tanigaki Riho、Takahashi Riku、Nguyen Mai Thanh Thi、Nguyen Nhan Trung、Do Truong Van Nhat、Nguyen Hai Xuan、Kataoka Takao
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 1 Pages: 26-33

    • DOI

      10.1248/bpb.b18-00457

    • NAID

      130007542227

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-01-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 4-O-Methylascochlorin inhibits the prolyl hydroxylation of hypoxia-inducible factor-1α, which is attenuated by ascorbate2019

    • Author(s)
      Kondo Tetsuya、Takeda Kenji、Muko Ryo、Ito Akihiro、Chang Young-Chae、Magae Junji、Kataoka Takao
    • Journal Title

      The Journal of Antibiotics

      Volume: 72 Issue: 5 Pages: 271-281

    • DOI

      10.1038/s41429-019-0157-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isolation of a spirolactone norditerpenoid as a yeast Ca^2+ signal transduction inhibitor from Kuji amber and evaluation of its effects on PPM1A activity2019

    • Author(s)
      Shimizu Eisaku、Koshino Hiroyuki、Noro Aoi、Maruyama Miku、Shimoda Nozomu、Uesugi Shota、Ohnishi Motoko、Kimura Ken-ichi
    • Journal Title

      Fitoterapia

      Volume: 134 Pages: 290-296

    • DOI

      10.1016/j.fitote.2019.02.027

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and <i>N</i>-Linked Glycosylation of Intercellular Adhesion Molecule-12018

    • Author(s)
      Baba K., Hiramatsu R., Suradej B., Tanigaki R., Koeda S., Waku T., Kataoka T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 12 Pages: 1757-1768

    • DOI

      10.1248/bpb.b18-00276

    • NAID

      130007539554

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-12-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kujigamberol interferes with pro-inflammatory cytokine-induced expression of and N-glycan modifications to cell adhesion molecules at different stages in human umbilical vein endothelial cells2018

    • Author(s)
      Fukuhara Sayuri、Tanigaki Riho、Kimura Ken-ichi、Kataoka Takao
    • Journal Title

      International Immunopharmacology

      Volume: 62 Pages: 313-325

    • DOI

      10.1016/j.intimp.2018.07.016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-allergy activities of Kuji amber extract and kujigamberol2018

    • Author(s)
      Maruyama M., Kobayashi M., Uchida T., Shimizu E., Higashio H., Ohno M., Uesugi S., Kimura KI.
    • Journal Title

      Fitoterapia

      Volume: 印刷中 Pages: 263-270

    • DOI

      10.1016/j.fitote.2018.02.033

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca2+-Signal Transduction Inhibitors, Kujiol A and Kujigamberol B, Isolated from Kuji Amber Using a Mutant Yeast2018

    • Author(s)
      Uchida Takeshi、Koshino Hiroyuki、Takahashi Shunya、Shimizu Eisaku、Takahashi Honoka、Yoshida Jun、Shinden Hisao、Tsujimura Maiko、Kofujita Hisayoshi、Uesugi Shota、Kimura Ken-ichi
    • Journal Title

      Journal of Natural Products

      Volume: 81 Issue: 4 Pages: 1070-1074

    • DOI

      10.1021/acs.jnatprod.7b00922

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Allantopyrone A interferes with multiple components of the TNF receptor 1 complex and blocks RIP1 modifications in the TNF-α-induced signaling pathway2017

    • Author(s)
      Quach Hue Tu、Tanigaki Riho、Yokoigawa Junpei、Yamada Yuriko、Niwa Masamitsu、Hirano Seiya、Shiono Yoshihito、Kimura Ken-ichi、Kataoka Takao
    • Journal Title

      The Journal of Antibiotics

      Volume: 70 Issue: 9 Pages: 929-936

    • DOI

      10.1038/ja.2017.74

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-κB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-α and the Fas Ligand2017

    • Author(s)
      Harada Misuzu、Morimoto Kyoko、Kondo Tetsuya、Hiramatsu Reiko、Okina Yuji、Muko Ryo、Matsuda Iyo、Kataoka Takao
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 12 Pages: 2603-2603

    • DOI

      10.3390/ijms18122603

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eudesmane-Type Sesquiterpene Lactones Inhibit Nuclear Translocation of the Nuclear Factor κB Subunit RelB in Response to a Lymphotoxin β Stimulation2017

    • Author(s)
      Quach Hue Tu、Kondo Tetsuya、Watanabe Megumi、Tamura Ryuichi、Yajima Yoshiki、Sayama Shinsei、Ando Masayoshi、Takao Kataoka
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 10 Pages: 1669-1677

    • DOI

      10.1248/bpb.b17-00170

    • NAID

      130006110549

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allantopyrone A activates the Keap1-Nrf2 pathway and protects from oxidative stress-induced cell death in PC12 cells2017

    • Author(s)
      Shota Uesugi, Makoto Muroi, Yasumitsu Kondoh, Yoshihito Shiono, Hiroyuki Osada, Ken-ichi Kimura
    • Journal Title

      The Journal of Antibiotics

      Volume: 70 Issue: 4 Pages: 429-434

    • DOI

      10.1038/ja.2016.99

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Yeast Ca2+-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca2+-influx2016

    • Author(s)
      Tomomi Abe, Miki Kobayashi, Yusuke Okawa, Tomoki Inui, Jun Yoshida, Hironori Higashio, Hisao Shinden, Shota Uesugi, Hiroyuki Koshino, Ken-ichi Kimura
    • Journal Title

      Fitoterapia

      Volume: 113 Pages: 188-194

    • DOI

      10.1016/j.fitote.2016.07.018

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Kujigamberolおよびその類縁体は炎症性サイトカイン誘導性の細胞接着因子の発現と糖鎖修飾に作用する2018

    • Author(s)
      谷垣 里穂、福原 早友里、木村 賢一、片岡 孝夫
    • Organizer
      2018年度日本農芸化学会関西支部大会第505回講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] NF-κBシグナル伝達経路とその標的遺伝子ICAM-1の発現に対する五環性トリテルペノイド類の作用機序の解析2018

    • Author(s)
      馬場 康輔、平松 令子、Benjamart Suradej、谷垣 里穂、小枝 清花、和久 友則、片岡 孝夫
    • Organizer
      2018年度日本農芸化学会関西支部大会第505回講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酵母を用いて久慈産琥珀から単離された高極性の新規抗アレルギー物質2018

    • Author(s)
      阿部 純平、越野 広雪、下田 希、高橋 穂乃香、新田 久男、木村 賢一
    • Organizer
      日本ケミカルバイオロジー学会第13回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 久慈産と他の日本産琥珀の生物活性物質、生物活性、並びにバイオマーカーの比較2018

    • Author(s)
      下田 希、川村 哲晃、清水 栄作、植田 直見、木村 賢一
    • Organizer
      日本農芸化学会2018年度北海道支部・東北支部合同大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] キナクリンはヒト肺がん腫A549細胞においてTNF-αおよびFasリガンドに対する感受性を増強する2018

    • Author(s)
      原田 美鈴、森元 今日子、近藤 哲也、平松 令子、翁 侑史、向 亮、松田 伊世、片岡 孝夫
    • Organizer
      日本農芸化学会2018年度(平成30年度)大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞接着因子ICAM-1の細胞内輸送に対するアシアチン酸の作用機序の解明2018

    • Author(s)
      馬場 康輔、平松 令子、片岡 孝夫
    • Organizer
      日本農芸化学会2018年度(平成30年度)大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TNF-αにより誘導されるNF-κBシグナル伝達経路に対する4-hydroxypanduratin Aとisopanduratin Aの作用機序の解析2018

    • Author(s)
      谷垣 里穂、Nguyen Thi Thanh Mai、Nguyen Trung Nhan、Do Van Nhat Truong、片岡 孝夫
    • Organizer
      日本農芸化学会2018年度(平成30年度)大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 非古典的NF-κBシグナル伝達経路に対するオイデスマン誘導体の作用機序の解析2017

    • Author(s)
      近藤 哲也、Quach Hue、渡辺 萌、田村 隆一、矢島 愛樹、佐山 信成、安東 政義、片岡 孝夫
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 炎症性サイトカインによって誘導される細胞接着因子に対するkujigamberolの作用機序の解明2017

    • Author(s)
      福原 早友里、木村 賢一、片岡 孝夫
    • Organizer
      日本農芸化学会2017年度(平成29年度)大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Allantopyrone A binds or crosslinks TNF receptor 1 and inhibits TNF-α-induced signaling pathway2017

    • Author(s)
      Hue Tu Quach, Junpei Yokoigawa, Yoshihito Shiono, Ken-ichi Kimura, Takao Kataoka
    • Organizer
      日本農芸化学会2017年度(平成29年度)大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞接着因子の発現誘導と糖鎖修飾に対する五環性トリテルペノイドの作用機序の解析2017

    • Author(s)
      平松 令子、馬場 康輔、片岡 孝夫
    • Organizer
      日本農芸化学会2017年度(平成29年度)大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素誘導因子の分子間相互作用や転写活性に対する4-O-メチルアスコクロリンの作用機序の解析2017

    • Author(s)
      近藤 哲也、武田 賢治、馬替 純二、片岡 孝夫
    • Organizer
      日本農芸化学会2017年度(平成29年度)大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 久慈産琥珀に含まれる生物活性物質の精製法の改良と新規物質の探索2017

    • Author(s)
      高橋 穂乃香、越野 広雪、川村 哲晃、清水 栄作、新田 久男、上杉 祥太、大野 美紗、木村 賢一
    • Organizer
      日本農芸化学会2017年度(平成29年度)大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] NF-κBサブユニットRelBの転写制御機構の解析2016

    • Author(s)
      渡辺 萌、竹内 文彦、片岡 孝夫
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Book] Bioprobes Biochemical Tools for Investigating Cell Function Second Edition Editor: Hiroyuki Osada2017

    • Author(s)
      Hiroyuki Osada、Nobumoto Watanabe、Akihiro Ito、Minoru Yoshida、Etsu Tashiro、Mitsuhiro Kitagawa、Masaya Imoto、Takao Kataoka、Hiroyuki Koshino、Takeo Usui
    • Total Pages
      384
    • Publisher
      Springer
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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