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Molecular mechanism in atheroprotective effects by the enzymes that control membrane sphingolipid levels

Research Project

Project/Area Number 16K15409
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionKanazawa University

Principal Investigator

ISHIMARU KAZUHIRO  金沢大学, 医学系, 協力研究員 (70595446)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords動脈硬化 / 老年医学 / スフィンゴ脂質代謝 / 動脈硬化症 / オートファジー
Outline of Final Research Achievements

In mice in which the metabolic enzyme was systematically deleted, atherosclerotic lesions were significantly increased by loading with a cholesterol diet. And, it was thought that the enzyme present in bone marrow-derived cells, particularly macrophages, were strongly involved. This enzyme might have atheroprotective role.
After macrophages take up unnecessary or modified lipids, they change to foam cells and deposit in arterial blood vessels followed by blood flow problems. By the analysis of lipid uptake and degradation functions, lipolysis-related autophagic pathways may be mainly impaired in enzyme deleted macrophages.

Academic Significance and Societal Importance of the Research Achievements

これまでにも全世界で動脈硬化治療薬の開発が行われて来たが、未だ画期的な治療薬は作出されて来なかった。新しい治療薬の開発の為には、新しい観点からの動脈硬化形成機序を明らかにする事が重要である。本研究により、スフィンゴ脂質代謝を制御する鍵酵素が持つ抗動脈硬化作用がオートファジー制御という新しい観点から発揮される事が判明した。これらは今後、新規動脈硬化治療法の開発基盤への有益な情報提供となる。

Report

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

    (13 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The class II phosphoinositide 3-kinases PI3K-C2α and PI3K-C2β differentially regulate clathrin-dependent pinocytosis in human vascular endothelial cells.2019

    • Author(s)
      Aung KT, Yoshioka K, Ishimaru K, Aki S, Takuwa N, and Takuwa Y.
    • Journal Title

      Journal of Physiological Sciences

      Volume: 69 Issue: 2 Pages: 263-280

    • DOI

      10.1007/s12576-018-0644-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Class II PI3Ks α nad β are required for Rho-dependent uterine smooth muscle contraction and parturition in mice.2019

    • Author(s)
      Sarker AK, Aki S, Yoshioka K, Kuno K, Okamoto Y, Ishimaru K, Takuwa N, and Takuwa Y.
    • Journal Title

      Endocrinology

      Volume: 160 Issue: 1 Pages: 235-248

    • DOI

      10.1210/en.2018-00756

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.2018

    • Author(s)
      Zhao J, Okamoto Y, Asano Y, Ishimaru K, Aki S, Yoshioka K, Takuwa N, Wada T, Inagaki Y, Takahashi C, Nishiuchi T, Takuwa Y.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 5 Pages: e0197604-e0197604

    • DOI

      10.1371/journal.pone.0197604

    • NAID

      120006605152

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MTMR4, a phosphoinositide specific 3’-phosphatase, regulates TFEB activity and the endocytic and autophagic pathways.2018

    • Author(s)
      Pham HQ, Yoshioka K, Mohri H, Nakata H, Aki S, Ishimaru K, Takuwa N, and Takuwa Y.
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 8 Pages: 670-687

    • DOI

      10.1111/gtc.12609

    • NAID

      120006621947

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] iNOS as a driver of inflammation and apoptosis in mouse skeletal muscle after burn injury: Possible involvement of sirt1 S- nitrosylation-mediated acetylation of p65 NFeΚB and p532017

    • Author(s)
      Nakazawa H, Chang K, Shinozaki S, Yasukawa T, Ishimaru K, Yasuhara S, Yu YM, Martyn JA, Tompkins RG, Shimokado K, Kaneki M
    • Journal Title

      PLoS One

      Volume: 12 Issue: 1 Pages: e0170391-e0170391

    • DOI

      10.1371/journal.pone.0170391

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Myotubularin-related protein 4 (MTMR4), a phosphoinositide 3'-phosphatase, regulates endolysosome integrity and autophagy flux in human lung alveolar epithelial A549 cells2018

    • Author(s)
      Pham Quynh Hoa, Yoshioka Kazuaki, Azadul Sarker Kabir, Aung Thuzar Khin, Islam Shahidul, Aki Sho, Ishimaru Kazuhiro, Takuwa Noriko, Takuwa Yoh
    • Organizer
      第 95 回日本生理学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Class II phosphoinositide 3-kinase isoforms PI3K-C2αand PI3K-C2β play essential roles in pinocytosis in vascular endothelial cells2018

    • Author(s)
      Aung Thuzar Khin, Yoshioka Kazuaki, Aki Sho, Pham Quynh Hoa, Sarker Kabir Azadul, Islam Shahidul, Ishimaru Kazuhiro, Takuwa Noriko, Takuwa Yoh
    • Organizer
      第 95 回日本生理学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Novel indispensable role of and isoforms of class II PI3K for uterine smooth muscle contraction and labor2018

    • Author(s)
      Azadul Kabir Sarker, Sho Aki, Kazuaki Yoshioka, Koji Kuno, Kazuhiro Ishimaru, Noriko Takuwa, Yoh Takuwa
    • Organizer
      第54回北陸生殖医学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] S1P2によるブレオマイシン誘発肺線維症の増悪機構の検討:肺胞マクロファージの細胞老化制御の関与2018

    • Author(s)
      多久和典子, 岡本安雄, 石丸和宏, 多久和陽
    • Organizer
      日本病態生理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Sphingosine Kinase 2 Inhibits Macrophage Cholesterol Accumulation and Atherosclerosis via Autophagy Stimulation2018

    • Author(s)
      Kazuhiro Ishimaru, Yoh Takuwa
    • Organizer
      American Heart Association 2018 Scientific Sessions
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Myotubularin-related protein 4 (MTMR4), a phosphoinositide 3'-phosphatase, regulates endolysosome integrity and autophagy flux in human lung alveolar epithelial A549 cells2018

    • Author(s)
      Pham Quynh Hoa, Yoshioka Kazuaki, Azadul Sarker Kabir, Aung Thuzar Khin, Islam Shahidul, Aki Sho, Ishimaru Kazuhiro, Takuwa Noriko, Takuwa Yoh
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Class II phosphoinositide 3-kinase isoforms PI3K-C2α and PI3K-C2β play essential roles in pinocytosis in vascular endothelial cells2018

    • Author(s)
      Aung Thuzar Khin, Yoshioka Kazuaki, Aki Sho, Pham Quynh Hoa, Sarker Kabir Azadul, Islam Shahidul, Ishimaru Kazuhiro, Takuwa Noriko, Takuwa Yoh
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗がん剤による臓器障害におけるスフィンゴシン-1-リン酸(S1P)情報伝達系の関与2017

    • Author(s)
      多久和 典子、石丸 和宏、岡本 安雄、多久和 陽
    • Organizer
      第27回日本病態生理学会大会
    • Related Report
      2017 Research-status Report

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

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