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The role of cellular localization of ALOX proteins in vascular aging

Research Project

Project/Area Number 15K09451
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNational Center for Geriatrics and Gerontology (2016-2018)
Hamamatsu University School of Medicine (2015)

Principal Investigator

KATSUMI Akira  国立研究開発法人国立長寿医療研究センター, 病院, 部長 (80378025)

Co-Investigator(Kenkyū-buntansha) 丸山 光生  国立研究開発法人国立長寿医療研究センター, その他部局等, 副所長 (00212225)
天野 睦紀  名古屋大学, 医学系研究科, 准教授 (90304170)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsRhoA / 脂質メディエーター / 細胞内輸送 / Rho / フォルミン / リポキシゲナーゼ / Rho GTPase / エフェクター / 血管老化 / Rhoファミリー / アラキドン酸リポキシゲナーゼ
Outline of Final Research Achievements

Rho family proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.To identify novel downstream effectors of RhoA, we performed GST-RhoA affinity column chromatography by using platelet lysates. Cytosol fraction of platelet was loaded onto affinity columns on which GST, GST-RhoA-N19, or GST-RhoA-L63 was immobilized. Using triple quadrupole liquid chromatography tandem mass spectrometer, several proteins associated with active RhoA were identified. Arachidonate lipoxygenase (ALOX) binds to GST-RhoA-L63, but not to GST-RhoA-N19 along with the known RhoA effectors. ALOX does not directly bind to RhoA-L63, although Daam1 is shown to bind to ALOX. The second LH2 domain of ALOX directly binds to N-terminal of Daam1, suggesting that Daam1 functions as a scaffolding protein for the assembly of ALOX. We further investigate the roles of Daam1 on ALOX activity and subcellular localization of these molecules.

Academic Significance and Societal Importance of the Research Achievements

アラキドン酸リポキシゲナーゼ(ALOX)とその下流の脂質メディエーターは動脈硬化、血小板凝集、慢性炎症、がんの進展などに関与する多機能蛋白である。ALOX下流の脂質メディエーターについては活発に研究が行われているが、上流の制御メカニズムについては殆ど報告がなされていなかった。当該研究ではLOXの細胞内局在をRho family GTPaseが制御しており、動脈硬化部位、免疫器官など多様な臓器に脂質メディエーターをリクルートする際にこの経路が重要であるという新たな知見を得た。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017 2015

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

  • [Journal Article] Apparent synonymous mutation F9 c.87A>G causes secretion failure by in-frame mutation with aberrant splicing.2019

    • Author(s)
      Odaira K, Tamura S, Suzuki, N Kakihara M, Hattori Y, Tokoro M, Suzuki S, Takagi A, Katsumi A, Hayakawa F, Okamoto S, Suzuki A, Kanematsu T, Matsushita T, Kojima T.
    • Journal Title

      Thrombosis Research

      Volume: in press

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular basis of SERPINC1 mutations in Japanese patients with antithrombin deficiency2019

    • Author(s)
      Tamura Shogo、Hashimoto Erika、Suzuki Nobuaki、Kakihara Misaki、Odaira Koya、Hattori Yuna、Tokoro Mahiru、Suzuki Sachiko、Takagi Akira、Katsumi Akira、Hayakawa Fumihiko、Suzuki Atsuo、Okamoto Shuichi、Kanematsu Takeshi、Matsushita Tadashi、Kojima Tetsuhito
    • Journal Title

      Thrombosis Research

      Volume: 178 Pages: 159-170

    • DOI

      10.1016/j.thromres.2019.04.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1-RUNX1T1 leukemia with t(8;12;21).2017

    • Author(s)
      Abe A, Yamamoto Y, Katsumi A, Okamoto A, Tokuda M, Inaguma Y, Yamamoto K, Yanada M, Kanie T, Tomita A, Akatsuka Y, Okamoto M, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      Int J Hematol.

      Volume: - Issue: 2 Pages: 208-212

    • DOI

      10.1007/s12185-017-2387-x

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro exploration of latent prothrombin mutants conveying antithrombin resistance.2017

    • Author(s)
      Tamura S, Murata-Kawakami M, Takagi Y, Suzuki S, Katsumi A, Takagi A, Kojima T.
    • Journal Title

      Thromb Res.

      Volume: 159 Pages: 33-38

    • DOI

      10.1016/j.thromres.2017.09.020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 後天性慢性赤芽球癆に対するABO 血液型一致同胞間骨髄移植後も赤血球造血のみ遅延した一例2017

    • Author(s)
      西田徹也、今橋真弓、今橋伸彦、大橋春彦、勝見 章、寺倉精太郎、村田 誠、清井 仁、直江知樹
    • Journal Title

      日本輸血細胞治療学会誌

      Volume: 63 Pages: 614-618

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 後天性慢性赤芽球癆に対するABO血液型一致 同胞間骨髄移植後も赤血球造血のみ遅延した一例2017

    • Author(s)
      西田徹也、今橋真弓、今橋伸彦、大橋春彦、勝見章、寺倉精太郎、村田誠、清井仁、直江知樹
    • Journal Title

      日本輸血細胞治療学会誌

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 臨床研究DBシステムD☆Dを用いた静脈血栓塞栓症の発症率推計2018

    • Author(s)
      勝見章,渡辺浩,松下正,小嶋哲人
    • Organizer
      第60回日本老年医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 臨床研究DBシステムD☆Dを用いた静脈血栓塞栓症の発症率推計2018

    • Author(s)
      勝見章,渡辺浩,松下正,小嶋哲人
    • Organizer
      第40回日本血栓止血学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Many of the prothrombin mutations in the sodium-binding region cause an antithrombin-resistance phenotype2018

    • Author(s)
      Shogo Tamura, Moe Murata-Kawakami, Yuki Takagi, Sachiko Suzuki, Akira Katsumi, Akira Takagi, Tetsuhito Kojima
    • Organizer
      The 10th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prevalence of venous thromboembolism (VTE) in a single institute2018

    • Author(s)
      Akira Katsumi, Seara Ikeno, Hiroshi Watanabe, Tadashi Matsushita, Tetsuhito Kojima
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Efficacy of Eculizumab for aplastic anemia developed to paroximal nocturnal hemogrobinuria after IST2018

    • Author(s)
      Seara Ikeno, Motohito Okabe, Yuka Kawaguchi, Marie Ohbiki, Yoonha Lee, Masahide Osaki, Miyo Goto, Hiroaki Araie, Takahiko Sato, Takanobu Morishita, Yukiyasu Ozawa, Akira Katsumi, Koichi Miyamura
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Arachidonate 12-lipoxygenase binds to active RhoA through Daam12017

    • Author(s)
      Moe Murata, Akira Katsumi, Katsuhiro Kato, Asami Matsuda, Tomoki Nishioka, Mutsuki Amano, Tadashi Matsushita, Hitoshi Kiyoi, Mitsuo Maruyama, Tetsuhito Kojima, Kozo Kaibuchi
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 皮疹によるボルテゾミブ中止後、カルフィルゾミブでInfusion reactionを発症した多発性骨髄腫の一例2017

    • Author(s)
      宮澤 憲治、勝見 章
    • Organizer
      第15回日本臨床腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規大欠失症例を含む先天性アンチトロンビン欠乏症のSERPINC1解析2017

    • Author(s)
      橋本恵梨華、高木夕希、鈴木幸子、坂根寛人、田村彰吾、高木明、金子誠、勝見章、松下正、小嶋哲人
    • Organizer
      第18回日本検査血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Arachidonate 12-lipoxygenase binds to active RhoA through Daam12017

    • Author(s)
      Moe Murata, Akira Katsumi, Katsuhiro Kato, Asami Matsuda, Tomoki Nishioka, Mutsuki Amano, Tadashi Matsushita, Hitoshi Kiyoi, Mitsuo Maruyama, Tetsuhito Kojima, Kozo Kaibuchi
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Rho H, a hematopoietic cell specific Rho protein, Deactivates Rac through T cell activation GTPase activating protein (TAGAP)2015

    • Author(s)
      Asami Matsuda , Akira Katsumi , Mutsuki Amano , Yasuyuki Nagata , Takaaki Ono , Mitsuo Maruyama , Hiroshi Kiyoi, Tomoki Naoe, Kozo Kaibuchi
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 血球特異的なRhoファミリー蛋白RhoHによるRacの不活性化機構はT細胞活性化GAP(TAGAP)を介する2015

    • Author(s)
      松田亜沙実、勝見 章、天野睦紀、永田泰之、小野孝明、大西一功、丸山光生、貝淵弘三、清井 仁、直江知樹
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ANAクラウンプラザホテル金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 血球特異的Rho ファミリー蛋白RhoH はT cell activation GTPase activating protein(TAGAP) を介し てRac を不活性化する2015

    • Author(s)
      松田亜沙実、勝見章、天野睦紀、永田泰之、大西一功、清井仁、直江知樹
    • Organizer
      第74 回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Cancer-Associated Thrombosis: an Overview2015

    • Author(s)
      勝見 章
    • Organizer
      第37回日本血栓止血学会学術集会 学術推進委員会(SPC)シンポジウム
    • Place of Presentation
      甲府市民会館
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Book] 日本臨牀76巻7 (2018 年8 月) 老年医学 XI.高齢者の臓器別疾患 悪性リンパ腫2018

    • Author(s)
      池野世新、勝見 章
    • Total Pages
      5
    • Publisher
      日本臨床社
    • Related Report
      2018 Annual Research Report
  • [Book] 静脈血栓塞栓症診断・治療マニュアル2015

    • Author(s)
      福田幾夫、勝見 章 など
    • Total Pages
      599
    • Publisher
      医薬ジャーナル社
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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