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Myocardial protection via mTOR - Proposal of novel therapy for ischemia-reperfusion injury

Research Project

Project/Area Number 17K11909
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

KITAHATA Hiroshi  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (60161486)

Co-Investigator(Kenkyū-buntansha) 高石 和美  徳島大学, 病院, 講師 (20325286)
川人 伸次  徳島大学, 大学院医歯薬学研究部(医学域), 特任教授 (60284296)
堤 保夫  広島大学, 大学院医系科学研究科(医), 教授 (90523499)
藤原 茂樹  徳島大学, 病院, 助教 (90434505)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords心筋保護 / 虚血再還流 / mTOR / rapamyacin / ロイシン / プレコンディショニング / 糖尿病モデル / 虚血再灌流 / rapamycin / ミトコンドリア
Outline of Final Research Achievements

Using isolated ventricular myocytes and ischemia-reperfusion in-vivo model of mouse, we investigated the mechanism of leucine's myocardial protection.
It was revealed that the myocardial protection of leucine is involved in the mammalian target of rapamycin (mTOR) -S6 Kinase pathway. This myocardial protection has a mechanism different from that of the insulin signal system and was also effective in diabetic model mice.

Academic Significance and Societal Importance of the Research Achievements

糖尿病罹患者は非罹患者に比べて虚血性心疾患の発症率が高いことが知られている。一方,短時間の虚血再灌流がその後の長時間の虚血に対する心筋梗塞サイズを減少させる現象,プレコンディショニング作用や吸入麻酔薬,オピオイドの投与による心筋保護作用のメカニズムは,インスリンシグナルと多くを共有しているため,高血糖モデルでは心筋保護効果が減弱してしまう。ロイシンによる心筋保護作用が,これらと異なるmTORを介した作用機序であり,糖尿病モデルでも有効であることが明らかになった.この結果は,糖尿病患者における心筋虚血予防の新しい治療法の確立および治療薬の開発の観点からも非常に重要であると思われる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (28 results)

All 2020 2019 2018 2017

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 11 results) Presentation (13 results) (of which Int'l Joint Research: 10 results)

  • [Journal Article] Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury.2020

    • Author(s)
      Satomi S, Morio A, Miyoshi H, Nakamura R, Tsutsumi R, Sakaue H, Yasuda T, Saeki N, Tsutsumi YM
    • Journal Title

      Life Science

      Volume: 245 Pages: 117368-117368

    • DOI

      10.1016/j.lfs.2020.117368

    • NAID

      120006993613

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrons released from both flavins of NADPH-P450 reductase contribute to the reductive mobilization of iron from ferritin2019

    • Author(s)
      Takaishi Kazumi、Kitahata Hiroshi
    • Journal Title

      The Journal of Medical Investigation

      Volume: 66 Issue: 3.4 Pages: 230-232

    • DOI

      10.2152/jmi.66.230

    • NAID

      130007732968

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Continuous blood glucose monitoring during pediatric cardiopulmonary bypass.2019

    • Author(s)
      Kakuta N, Kawahito S, Mita N, Soga T, Yagi S, Satomi S, Tada F, Kinoshita H, Takaishi K, Kitahata H
    • Journal Title

      Clinical Pediatric Anesthesia

      Volume: 25 Pages: 3-7

    • NAID

      120006768427

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accuracy and reliability of continuous blood glucose monitoring during pediatric cardiopulmonary bypass.2019

    • Author(s)
      Kawahito S, Mita N, Soga T, Yagi S, Kakuta N, Satomi S, Kinoshita H, Takaishi K, Kitagawa T, Kitahata H
    • Journal Title

      Journal of Artificial Organs

      Volume: 22 Issue: 4 Pages: 353-356

    • DOI

      10.1007/s10047-019-01111-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring of muscle mass in critically ill patients: comparison of ultrasound and two bioelectrical impedance analysis devices.2019

    • Author(s)
      Nobuto Nakanishi, Rie Tsutsumi, Yoshihiro Okayama, Takuya Takashima, Yoshitoyo Ueno, Taiga Itagaki, Yasuo Tsutsumi, Hiroshi Sakaue, and Jun Oto.
    • Journal Title

      Journal of Intensive Care

      Volume: 7 Issue: 1 Pages: 61-61

    • DOI

      10.1186/s40560-019-0416-y

    • NAID

      120006939635

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GaN Schottky barrier diodes with nickel nitride anodes sputtered at different nitrogen partial pressure2019

    • Author(s)
      Li Xiaobo、Pu Taofei、Taiki Hoshi、Zhang Tong、Xie Tian、Luke Fujiwara Shigeki Joseph、Kitahata Hiroshi、Li Liuan、Kobayashi Sachio、Ito Motoo、Li Xianjie、Ao Jin-Ping
    • Journal Title

      Vacuum

      Volume: 162 Pages: 72-77

    • DOI

      10.1016/j.vacuum.2019.01.030

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Noninvasive continuous blood pressure monitoring by the ClearSight system during robot‐assisted laparoscopic radical prostatectomy2018

    • Author(s)
      Yoko Sakai, Yasuo M. Tsutsumi, Takuro Oyama, Chiaki Murakami, Nami Kakuta, Katsuya Tanaka
    • Journal Title

      The Journal of Medical Investigation

      Volume: 65 Issue: 1.2 Pages: 69-73

    • DOI

      10.2152/jmi.65.69

    • NAID

      130006575619

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of using non‐invasive continuous arterial pressure monitoring with ClearSight in hemodynamic monitoring during living renal transplantation in a recipient:a case report2018

    • Author(s)
      Nami Kakuta, Yasuo M. Tsutsumi, Chiaki Murakami, Yoko Sakai, Takuro Oyama, Asuka Kasai, Katsuyoshi Kume, Katsuya Tanaka
    • Journal Title

      The Journal of Medical Investigation

      Volume: 65 Issue: 1.2 Pages: 139-141

    • DOI

      10.2152/jmi.65.139

    • NAID

      130006575564

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nasotracheal intubation through pharyngeal flap after pharyngeal flap construction2018

    • Author(s)
      Takaishi Kazumi、Kawahito Shinji、Fujiwara Shigeki、Kitahata Hiroshi
    • Journal Title

      J Clin Anesth

      Volume: 44 Pages: 121-122

    • DOI

      10.1016/j.jclinane.2017.11.026

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 心筋保護作用と神経体液性因子2018

    • Author(s)
      里見志帆,堤保夫
    • Journal Title

      循環制御

      Volume: 39 Pages: 162-164

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The unique action of nicorandil on cerebral circulation2018

    • Author(s)
      Kinoshita Hiroyuki、Kawahito Shinji、Takaishi Kazumi
    • Journal Title

      Journal of Anesthesia

      Volume: 32 Issue: 3 Pages: 1-1

    • DOI

      10.1007/s00540-018-2499-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury2017

    • Author(s)
      Naoji Mita, Shinji Kawahito, Tomohiro Soga, Kazumi Takaishi, Hiroshi Kitahata, Munehide Matsuhisa, Mitsuo Shimada, Hiroyuki Kinoshita, Yasuo M Tsutsumi, Katsuya Tanaka
    • Journal Title

      Journal of Artificial Organs

      Volume: 1 Issue: 1 Pages: 76-83

    • DOI

      10.1007/s10047-016-0925-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tissue oxygenation index reflects changes in forearm blood flow after brief ischemia2017

    • Author(s)
      Kinoshita Hiroyuki、Akahori Takahiko、Nakamura Emi、Okawa Hazuki、Kawahito Shinji、Kitahata Hiroshi、Fujiwara Yoshihiro
    • Journal Title

      The Journal of Medical Investigation

      Volume: 64 Issue: 3.4 Pages: 228-232

    • DOI

      10.2152/jmi.64.228

    • NAID

      130006105185

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of oral carbohydrate with amino acid solution on serum oxidative/anti-oxidative status in healthy volunteers2017

    • Author(s)
      Yasuo M. Tsutsumi, Takuro Oyama, Nami Kakuta, Yousuke T. Horikawa, Katsuyoshi Kume, Yoko Sakai, Rie Tsutsumi, and Katsuya Tanaka.
    • Journal Title

      J Anesth

      Volume: 31 Issue: 3 Pages: 472-475

    • DOI

      10.1007/s00540-017-2355-x

    • NAID

      40021224363

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Comparison of Fosaprepitant and Ondansetron for Preventing Postoperative Nausea and Vomiting in Moderate to High Risk Patients: A Retrospective Database Analysis2017

    • Author(s)
      Chiaki Murakami, Nami Kakuta, Katsuyoshi Kume, Yoko Sakai, Asuka Kasai, Takuro Oyama, Katsuya Tanaka, and Yasuo M. Tsutsumi
    • Journal Title

      Biomed Res Int

      Volume: 2017 Pages: 1-5

    • DOI

      10.1155/2017/5703528

    • NAID

      120006535022

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Pleth Variability Index Predicts Hemodynamic Derangements In Patients Undergoing Oral Surgery.2019

    • Author(s)
      Takaishi K, Aoyama T, Fujiwara S, Otsuka R, Eguchi S, Tsutsumi Y, Kawahito S, Kinoshita H, Kitahata H
    • Organizer
      The Anesthesiology 2019 Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Normally-off AIGaN/GaN heterojunction field-effect transistors.2019

    • Author(s)
      Pu T, Wang X, Huang Q, Li X, Bu Y, Fujiwara JL S, Kitahata H, Ao JP
    • Organizer
      6th International Symposium on 2019 Single Crystal Diamond and Electronics
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High resolution via-hole etching technique for silicon carbon substrate.2019

    • Author(s)
      Li Y, Nakao S, Fujiwara JL S, Aoki K, Kitahata H, Ao JP
    • Organizer
      6th International Symposium on 2019 Single Crystal Diamond and Electronics
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microwave wireless power transfer system for small medical equipment.2019

    • Author(s)
      Nakao S, Fujiwara JL S, Li Y, Aoki K, Kitahata H, Ao JP
    • Organizer
      6th International Symposium on 2019 Single Crystal Diamond and Electronics
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fabrication and clinical application of a wireless-power-transmission-type medical device.2019

    • Author(s)
      Fujiwara JL S, Nakao S, Li Y, Ao JP, Takaishi K, Kitahata H
    • Organizer
      Euroanaesthesia 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rapamycin becomes the sevoflurane vasodilator effect apparent in the rat artery.2018

    • Author(s)
      Kazumi Takaishi, Shiho Satomi, Naoji Mita, Takeshi Yamamoto, Ryo Otsuka, Satoru Eguchi, Shigeki Joseph Luke Fujiwara, Shinji Kawahito, Hiroyuki Kinoshita, Hiroshi Kitahata
    • Organizer
      The 15th International Dental Congress on Anesthesia, Sedation and Pain Control
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Three-dimensional computed tomography and nasopharyngoscopy for nasotracheal intubation after pharyngeal flap construction.2018

    • Author(s)
      Takeshi Yamamoto, Kazumi Takaishi, Ryo Otsuka, Shigeki Joseph Luke Fujiwara, Satoru Eguchi, Tomohiro Soga, Shinji Kawahito, Hiroshi Kitahata
    • Organizer
      The 15th International Dental Congress on Anesthesia, Sedation and Pain Control
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Influence of PTS stopcock status on the natural frequency of blood pressure-transduer kits.2018

    • Author(s)
      Shigeki Joseph Luke Fujiwara, Keiichi Tachihara, Satoshi Mori, Ryo Otsuka, Takeshi Yamamoto, Satoru Eguchi, Kazumi Takaishi, Izumi Toyoguchi, Jin-Ping Ao, Hiroshi Kitahata
    • Organizer
      The 15th International Dental Congress on Anesthesia, Sedation and Pain Control
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Glucose transporter-4 mediates acute isoflurane-induced preconditioning in vivo rabbits.2018

    • Author(s)
      Takuro Oyama, Yuta Uemura, Nami Kakuta, Yasuo M. Tsutsumi, Katsuya Tanaka
    • Organizer
      The Annual Meeting of the American Society of Anesthesiologists
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of clinical sevoflurane doses as both the protein kinase C activator and NADPH oxidase inhibitor upon thromboxane A2 application in the rat Arteries.2017

    • Author(s)
      Shiho Satomi, Kazumi Takaishi, Shinji Kawahito, Hiroshi Kitahata, Katsuya Tanaka, Hiroyuki Kinoshita
    • Organizer
      The Annual Meeting of the American Society of Anesthesiologists
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of jelly type carbohydrate on metabolism and evaluation of its excretion in healthy subjects.2017

    • Author(s)
      Takuro Oyama, Nami Kakuta, Asuka Kasai, Naoji Mita, Katsuyoshi Kume, Katsuya Tanaka, and Yasuo M. Tsutsumi
    • Organizer
      The Annual Meeting of the American Society of Anesthesiologists
    • Related Report
      2017 Research-status Report
  • [Presentation] The effect of intraoperative glucose load on metabolism in patients with diabetes mellitus.2017

    • Author(s)
      Asuka Kasai, Kohei Fukuta, Katsuya Tanaka, Nami Kakuta, and Yasuo M. Tsutsumi
    • Organizer
      The Annual Meeting of the American Society of Anesthesiologists
    • Related Report
      2017 Research-status Report
  • [Presentation] The influence of glucose load on metabolism in elderly patients during surgery using remifentanil-induced anesthesia.2017

    • Author(s)
      Kohei Fukuta, Asuka Kasai, Katsuya Tanaka, Yoko Sakai, and Yasuo M. Tsutsumi
    • Organizer
      The Annual Meeting of the American Society of Anesthesiologists
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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