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Novel anti-muscle atrophy signaling via the stress response molecule HO-1

Research Project

Project/Area Number 20K19639
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionThe University of Tokushima

Principal Investigator

UCHIDA Takayuki  徳島大学, 大学院医歯薬学研究部(医学域), 講師 (00803561)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords筋萎縮 / 鉄代謝 / ミトコンドリア / HO-1 / 筋肉 / 酸化ストレス
Outline of Research at the Start

骨格筋量は加齢や運動負荷の減少(寝たきりなどのunloading環境)によって低下することが知られている。これら筋萎縮の誘導因子についてはミトコンドリアの機能低下や酸化ストレスの産生亢進、鉄代謝異常など様々な報告が為されている。しかし、未だ筋萎縮発生メカニズムの全容は不明な点が多く、筋萎縮に対する根本的な治療法は存在しない。そこで本研究では、抗酸化因子として知られるHO-1に着目して、これらの代謝異常が引き起こされるメカニズムを解明し、HO-1を介した筋萎縮治療法について検証する。

Outline of Final Research Achievements

To maintain skeletal muscle mass, the relationship between iron metabolism and mitochondrial metabolism is crucial. Previous studies have demonstrated that iron deficiency leads to mitochondrial dysfunction and abnormalities in muscle cells. In this study, we investigated how fluctuations in iron levels affect muscle cell metabolism. The results revealed that treatment with the iron chelator DFO resulted in a decrease in mitochondrial proteins and an imbalance in protein synthesis in muscle cells, leading to reduced muscle function. Furthermore, in a muscle atrophy model, it was observed that changes in iron levels affected the expression of muscle atrophy-related genes. These findings suggest that the interplay between iron metabolism and mitochondrial metabolism in muscle cells may contribute to the development of muscle atrophy.

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、鉄・エネルギー代謝異常から筋萎縮へと繋がる新規経路が明らかになり、大きな学術的意義を持つ。さらに、萎縮環境における鉄付加で筋萎縮抑制傾向がみられたことは、寝たきり状態や消耗性疾患等による筋萎縮を予防するために、食事やサプリメントとしての鉄付加が有効である可能性を示唆しており、社会的意義も大きい。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (9 results)

  • [Journal Article] Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise2022

    • Author(s)
      Madoka Kohno, Anayt Ulla, Rina Taniguchi, Akane Ohishi, Kako Hirayama, Yuma, Takemura, Shoichiro Takao, Yuki Kanazawa, Yuki Matsumoto, Masafumi Harada, Tomoya Fukawa, Hiro-Omi Kanayama, Takayuki Uchida, Toshio Suzuki, Takeshi Nikawa.
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 68 Issue: 6 Pages: 521-526

    • DOI

      10.3177/jnsv.68.521

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2022-12-31
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy2022

    • Author(s)
      Kitahata Kanako、Uchida Takayuki、Taniguchi Runa、Kato Ayano、Sugiura Kosuke、Sakakibara Iori、Oarada Motoko、Fukawa Tomoya、Junsoo Park、Inho Choi、Nikawa Takeshi
    • Journal Title

      The Journal of Medical Investigation

      Volume: 69 Issue: 1.2 Pages: 127-134

    • DOI

      10.2152/jmi.69.127

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Morin improves dexamethasone-induced muscle atrophy by modulating atrophy-related genes and oxidative stress in female mice2022

    • Author(s)
      Anayt Ulla, Kanae Osaki, Md Mizanur Rahman, Reiko Nakao, Takayuki Uchida, Isafumi Maru, Kazuaki Mawatari, Tomoya Fukawa, Hiro-Omi Kanayama, Iori Sakakibara, Katsuya Hirasaka, Takeshi Nikawa
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 86 Issue: 10 Pages: 1448-1458

    • DOI

      10.1093/bbb/zbac140

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal2022

    • Author(s)
      Adachi Yuichiro、Masuda Masashi、Sakakibara Iori、Uchida Takayuki、Niida Yuki、Mori Yuki、Kamei Yuki、Okumura Yosuke、Ohminami Hirokazu、Ohnishi Kohta、Yamanaka-Okumura Hisami、Nikawa Takeshi、Taketani Yutaka
    • Journal Title

      Life Science Alliance

      Volume: 5 Issue: 7 Pages: e202101345-e202101345

    • DOI

      10.26508/lsa.202101345

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Proteome Analysis in Response to Glucose Concentration in C2C12 Myotubes2022

    • Author(s)
      Ayano Kato,Iori Sakakibara,Taku Fukushima,Kosuke Sugiura,Tomoya Fukawa,Takeshi Nikawa and Takayuki Uchida
    • Journal Title

      Applied sciences

      Volume: 12 Issue: 3 Pages: 1553-1553

    • DOI

      10.3390/app12031553

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptome Analyses of In Vitro Exercise Models by Clenbuterol Supplementation or Electrical Pulse Stimulation2021

    • Author(s)
      Fukushima Taku、Takata Miho、Kato Ayano、Uchida Takayuki、Nikawa Takeshi、Sakakibara Iori
    • Journal Title

      Applied Sciences

      Volume: 11 Issue: 21 Pages: 10436-10436

    • DOI

      10.3390/app112110436

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle2021

    • Author(s)
      Nakao Reiko、Shen Weilin、Shimajiri Yasuka、Kainou Kumiko、Sato Yuki、Ulla Anayt、Ohnishi Kohta、Ninomiya Miyuki、Ohno Ayako、Uchida Takayuki、Tanaka Mitsuru、Akama Kazuhito、Matsui Toshiro、Nikawa Takeshi
    • Journal Title

      npj Science of Food

      Volume: 5 Issue: 1 Pages: 25-34

    • DOI

      10.1038/s41538-021-00108-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MuRF1 Deficiency Prevents Age‐Related Fat Weight Gain, Possibly Through Accumulation of PDK4 in Skeletal Muscle Mitochondria in Older Mice2021

    • Author(s)
      Sugiura Kosuke、Hirasaka Katsuya、Maeda Tasuku、Uchida Takayuki、Kishimoto Koji、Oarada Motoko、Labeit Siegfried、Ulla Anayt、Sakakibara Iori、Nakao Reiko、Sairyo Koichi、Nikawa Takeshi
    • Journal Title

      Journal of Orthopaedic Research

      Volume: - Issue: 5 Pages: 1026-1038

    • DOI

      10.1002/jor.25131

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Morin attenuates dexamethasone-mediated oxidative stress and atrophy in mouse C2C12 skeletal myotubes2021

    • Author(s)
      Ulla Anayt、Uchida Takayuki、Miki Yukari、Sugiura Kosuke、Higashitani Atsushi、Kobayashi Takeshi、Ohno Ayako、Nakao Reiko、Hirasaka Katsuya、Sakakibara Iori、Nikawa Takeshi
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 704 Pages: 108873-108873

    • DOI

      10.1016/j.abb.2021.108873

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Astaxanthin Prevents Atrophy in Slow Fiber Muscles by Inhibiting Mitochondrial Reactive Oxygen Species Via a Mitochondria-Mediated Apoptosis Pathwa2021

    • Author(s)
      Luchuanyang Sun, Nobuyuki Miyaji, Min Yang, Edward M Mills, Shigeto Taniyama, Takayuki Uchida, Takeshi Nikawa, Jifeng Li, Jie Shi, Katsuyasu Tachibana, Katsuya Hirasaka
    • Journal Title

      Nutrients

      Volume: 13 Issue: 2 Pages: 379-379

    • DOI

      10.3390/nu13020379

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 高脂肪食負荷によるMfn2と骨格筋エネルギー代謝の関連解明2022

    • Author(s)
      新垣 翼, 谷口 瑠菜, 青木 栄理香, 佐藤 文香, 高田 実穂, 内田 貴之, 二川 健
    • Organizer
      第76回 日本栄養食糧学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 廃用性筋萎縮におけるアコニターゼ活性の低下とその栄養学的保護2022

    • Author(s)
      山崎 穂, 松木 大揮, 中野 亘, 杉浦 宏祐, 布川 朋也, 内田 貴之, 榊原 伊織, 二川 健
    • Organizer
      第76回 日本栄養食糧学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 骨格筋におけるAconitase2の機能解明2022

    • Author(s)
      高田 実穂, 榊原 伊織, 岸田 昴大, 福島 拓, 新垣 翼, 内田 貴之, 布川 朋也, 二川 健
    • Organizer
      第76回 日本栄養食糧学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Mitofusin 2を介した筋内Ca2+-ROSシグナルの変化2021

    • Author(s)
      谷口瑠菜, 藤岡大樹, 内田貴之, 二川健
    • Organizer
      日本宇宙生物科学会第35回大会
    • Related Report
      2021 Research-status Report
  • [Presentation] ピセアタンノールの筋萎縮抑制効果の検討2020

    • Author(s)
      川端いずみ、内田貴之、加藤彩乃、Anaytulla、内田裕子、森貞夫、森田稔、二川健
    • Organizer
      第74回日本栄養・食糧学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 細胞内エネルギー代謝が筋繊維タイプに与える影響2020

    • Author(s)
      加藤彩乃、内田貴之、杉浦宏祐、池田泰隆、濱田広一郎、二川健
    • Organizer
      第74回日本栄養・食糧学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Unloadingによる筋萎縮におけるCa2+-ROSシグナルの変化2020

    • Author(s)
      藤岡大樹、内田貴之、杉浦宏祐、小林剛、東谷篤志、曽我部正博、二川健
    • Organizer
      第74回日本栄養・食糧学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 筋肉におけるミトコンドリアタンパク質Mfn2の役割2020

    • Author(s)
      内田貴之、三木裕加里、杉浦宏祐、真板綾子、中尾玲子、平坂勝也、東谷篤志、小林剛、曽我部正博、二川健
    • Organizer
      第74回日本栄養・食糧学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ミトコンドリア-小胞体接触領域(MAM)は廃用性筋萎縮を制御する2020

    • Author(s)
      西良浩一、杉浦宏祐、内田貴之、二川健
    • Organizer
      第93回日本整形外科学会学術総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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