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The elucidation of the molecular mechanisms of NO-mediated muscle atrophy

Research Project

Project/Area Number 21300149
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

TAKEDA Shin ichi  独立行政法人国立精神・神経医療研究センター, 神経研究所遺伝子疾患治療研究部, 部長 (90171644)

Co-Investigator(Kenkyū-buntansha) SUZUKI Yuuko  独立行政法人国立精神・神経医療研究センター, 神経研究所遺伝子疾患治療研究部, 室長 (00342931)
IMAMURA Michihiro  独立行政法人国立精神・神経医療研究センター, 神経研究所遺伝子疾患治療研究部, 室長 (80221787)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2009: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords骨格筋 / 筋萎縮 / 一酸化窒素 / 神経型一酸化窒素合成酵素 / 筋肥大 / 萎縮 / 筋ジストロフィー / nNOS / ニトロシル化
Research Abstract

We found that nNOS was involved in not only in the unload-induced muscle atrophy, but also in the overload-induced muscle hypertrophy. nNOS was immediately activated by mechanical overload, and this activation promoted formation of peroxynitrite, a reaction product of nitric oxide with superoxide, which was derived from NADPH oxidase 4(NOX4). These findings may develop therapeutics for muscle atrophy by targeting NO/peroxynitrite.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (45 results)

All 2012 2011 2010 2009

All Journal Article (16 results) (of which Peer Reviewed: 15 results) Presentation (22 results) Book (3 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Slow-dividing satellite cells retain long-term self-renewal ability in adult muscle2012

    • Author(s)
      Ono Y, Masuda S, Nam HS, Benezra R, Miyagoe-Suzuki Y, Takeda S., Corresponding author
    • Journal Title

      J Cell Sci

      Volume: 125 Issue: 5 Pages: 1309-1317

    • DOI

      10.1242/jcs.096198

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle2011

    • Author(s)
      Uezumi A, Ito T, Morikawa D, Shimizu N, Yoneda T, Segawa M, Yamaguchi M, Ogawa R, Matev MM, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Tsuchida K, Yamamoto H, Fukada S
    • Journal Title

      J Cell Sci

      Volume: 124(21) Issue: 21 Pages: 3654-3664

    • DOI

      10.1242/jcs.086629

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers2011

    • Author(s)
      F ukada S, Yamaguchi M, Kokubo H, Ogawa R, Uezumi A, Yoneda T, Matev MM, Motohashi N, Ito T, Zolkiewska A, Johnson RL, Saga Y, Miyagoe-Suzuki Y, Tsujikawa K, Takeda S, Yamamoto H
    • Journal Title

      Development

      Volume: 138 Issue: 21 Pages: 4609-4619

    • DOI

      10.1242/dev.067165

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MURF1 deficiency suppresses unloading-induced effects on osteoblasts and osteoclasts to lead to bone loss2011

    • Author(s)
      Kondo H, Ezura Y, Nakamoto T, Hayata T, Notomi T, Sorimachi H, Takeda S, Noda M
    • Journal Title

      J Cell Biochem

      Volume: 112(12) Issue: 12 Pages: 3525-30

    • DOI

      10.1002/jcb.23327

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Muscle-Specific MicroRNAs in Serum of Muscular Dystrophy Animal Models : Promising Novel Blood-Based Markers for Muscular Dystrophy2011

    • Author(s)
      M izuno H, Nakamura A, Aoki Y, Ito N, Kishi S, Yamamoto K, Sekiguchi M, Takeda S, Hashido K
    • Journal Title

      PLoS One

      Volume: 30 Issue: 3 Pages: e18388-e18388

    • DOI

      10.1371/journal.pone.0018388

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Matrix metalloproteinase-2 ablation in dystrophin-deficient mdx muscles reduces angiogenesis resulting in impaired growth of regenerated muscle fibers2011

    • Author(s)
      M iyazaki D, Nakamura A, Fukushima K, Yoshida K, Takeda S, Ikeda S
    • Journal Title

      Hum Mol Genet

      Volume: 20 Issue: 9 Pages: 1787-1799

    • DOI

      10.1093/hmg/ddr062

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crosstalk between Glucocorticoid Receptor and Nutritional Sensor mTOR in Skeletal Muscle2011

    • Author(s)
      S himizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S, Nakae J, Tagata Y, Nishitani S, Takehana K, Sano M, Fukuda K, Suematsu M, Morimoto C, Tanaka H
    • Journal Title

      Cell Metab

      Volume: 13 Issue: 2 Pages: 170-182

    • DOI

      10.1016/j.cmet.2011.01.001

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MURF1 deficiency suppresses unloading-induced effects on osteoblasts and osteoclasts to lead to bone loss2011

    • Author(s)
      Kondo H, et.al.
    • Journal Title

      Gene Ther

      Volume: 18 Issue: 9 Pages: 910-919

    • DOI

      10.1038/gt.2011.36

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crosstalk between Glucocorticoid Receptor and Nutritional Sensor mTOR in Skeletal Muscle.2011

    • Author(s)
      Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S, Nakae J, Tagata Y, Nishitani S, Takehana K, Sano M, Fukuda K, Suematsu M, Morimoto C, Tanaka H
    • Journal Title

      Cell Metab.

      Volume: 13 Pages: 170-182

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle2010

    • Author(s)
      Uezumi A, Fukuda S, Yamamoto N, Takeda S, Tsuchida K
    • Journal Title

      Nat Cell Biol

      Volume: 12 Issue: 2 Pages: 143-152

    • DOI

      10.1038/ncb2014

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle2010

    • Author(s)
      Uezumi A, Fukuda S, Yamamoto N, Takeda S, Tsuchida K
    • Journal Title

      Nat Cell Biol. 12

      Pages: 143-52

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin ligase Cbl-b is a negative regulator for IGF-1 signaling during muscle atrophy caused by unloading2009

    • Author(s)
      N akao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T
    • Journal Title

      Mol Cell Biol

      Volume: 17 Issue: 17 Pages: 4798-4811

    • DOI

      10.1128/mcb.01347-08

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells2009

    • Author(s)
      C hang H, Yoshimoto M, Umeda K, Iwasa T, Mizuno Y, Fukada S, Yamamoto H, Motohashi N, Miyagoe-Suzuki Y, Takeda S, Heike T, Nakahata T
    • Journal Title

      FASEB J

      Volume: 23 Issue: 6 Pages: 1907-1919

    • DOI

      10.1096/fj.08-123661

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin ligase Cbl-b is a negative regulator for IGF-1 signaling during muscle atrophy caused by unloading2009

    • Author(s)
      Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T
    • Journal Title

      Mol Cell Biol. 17

      Pages: 4798-4811

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells2009

    • Author(s)
      Chang H, Yoshimoto M, Umeda K, Iwasa T, Mizuno Y, Fukada S, Yamamoto H, Motohashi N, Miyagoe-Suzuki Y, Takeda S, Heike T, Nakahata T
    • Journal Title

      FASEB J. 23

      Pages: 1907-1919

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      鈴木友子, 武田伸一
    • Journal Title

      骨格筋, 炎症・再生医学事典(朝倉書店)

      Pages: 453-456

    • Related Report
      2009 Annual Research Report
  • [Presentation] Molecular mechanism of muscle hypertrophy-NO/peroxynitrite-induced activation of TRPV1-2012

    • Author(s)
      Takeda S
    • Organizer
      University of Geneva
    • Place of Presentation
      Geneva, Switzerland
    • Year and Date
      2012-03-21
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular mechanism of muscle hypertrophy-NO/peroxynitrite-induced activation of TRPV1-2012

    • Author(s)
      Takeda S
    • Organizer
      University of Geneva
    • Place of Presentation
      University of Geneva, Geneva, Switzerland(招待講演)
    • Year and Date
      2012-03-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨格筋神経型一酸化窒素合成酵素(nNOS)は過負荷によって活性化され,タンパク質合成の活性化を介して筋肥大の進行を制御している2011

    • Author(s)
      伊藤尚基,工藤明,鈴木友子,武田伸一
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨格筋神経型一酸化窒素合成酵素(nNOS)は過負荷によって活性化され,タンパク質合成の活性化を介して筋肥大の進行を制御している2011

    • Author(s)
      伊藤尚基
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Year and Date
      2011-12-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] nNOS is an essential mediator for mechanical overload-induced muscle hypertrophy2011

    • Author(s)
      N Ito, K. Akira, Y Suzuki, U Ruegg, S Takeda
    • Organizer
      International Conference On Muscle Wasting
    • Place of Presentation
      Ascona, Switzerland
    • Year and Date
      2011-09-20
    • Related Report
      2011 Final Research Report
  • [Presentation] nNOS is an essential mediator for mechanical overload-induced muscle hypertrophy2011

    • Author(s)
      N Ito
    • Organizer
      International Conference On Muscle Wasting
    • Place of Presentation
      Centro Stefano Franscini, Ascona, Switzerland
    • Year and Date
      2011-09-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨格筋の幹細胞と再生の分子機構2011

    • Author(s)
      武田伸一
    • Organizer
      第3回シグナルネットワーク研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-27
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨格筋の幹細胞と再生の分子機構2011

    • Author(s)
      武田伸一
    • Organizer
      第3回シグナルネットワーク研究会
    • Place of Presentation
      東京大学医科学研究所,東京(招待講演)
    • Year and Date
      2011-05-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of a long-term self-renewable population in activated satellite cells. The molecular and cellular mechanisms regulating skeletal muscle, development and regeneration2011

    • Author(s)
      O no Y, Masuda S, Miyagoe-Suzuki Y, Takeda S
    • Organizer
      EMBO conference series
    • Place of Presentation
      Wiesbaden, Germany
    • Year and Date
      2011-05-13
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of a long-term self-renewable population in activated satellite cells2011

    • Author(s)
      Ono Y
    • Organizer
      The molecular and cellular mechanisms regulating skeletal muscle, development and regeneration, EMBO conference series
    • Place of Presentation
      DORINT PALLAS HOTEL Wiesbaden, Germany
    • Year and Date
      2011-05-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Isolation and characterization of a long-term self-renewable population in activated satellite cells2011

    • Author(s)
      Takeda S
    • Organizer
      4^<th> International congress of Myology
    • Place of Presentation
      Lille, France
    • Year and Date
      2011-05-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Isolation and characterization of a long-term self-renewable population in activated satellite cells2011

    • Author(s)
      Takeda S
    • Organizer
      4^<th> International congress of Myology
    • Place of Presentation
      Lille Grand Palais, France(招待講演)
    • Year and Date
      2011-05-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨格筋神経型一酸化窒素合成酵素(nNOS)過負荷によって活性化され,タンパク質合成の活性化を介して筋肥大の進行を制御している2010

    • Author(s)
      伊藤尚基,工藤明,鈴木友子,武田伸一
    • Organizer
      第33回日本分子生物学会年会,第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨格筋神経型一酸化窒素合成酵素(nNOS)過負荷によって活性化され, タンパク質合成の活性化を介して筋肥大の進行を制御している.2010

    • Author(s)
      伊藤尚基, 工藤明, 鈴木友子, 武田伸一
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸神戸ポートアイランド
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] nNOSは筋萎縮と筋肥大を制御するメカノセンサーである2010

    • Author(s)
      武田伸一,伊藤尚基,鈴木友子
    • Organizer
      第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report
  • [Presentation] nNOSは筋萎縮と筋肥大を制御するメカノセンサーである.2010

    • Author(s)
      武田伸一, 伊藤尚基, 鈴木友子
    • Organizer
      第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸神戸ポートアイランド
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨格筋神経型一酸化窒素合成酵素は過負荷によって活性化され、タンパク質合成・分解の制御を介して筋肥大を促進する2010

    • Author(s)
      伊藤尚基,工藤明,鈴木友子,武田伸一
    • Organizer
      第31回日本炎症・再生医学会
    • Place of Presentation
      新宿
    • Year and Date
      2010-08-05
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨格筋神経型一酸化窒素合成酵素は過負荷によって活性化され、タンパク質合成・分解の制御を介して筋肥大を促進する.2010

    • Author(s)
      伊藤尚基, 工藤明, 鈴木友子, 武田伸一
    • Organizer
      第31回日本炎症・再生医学会
    • Place of Presentation
      新宿京王プラザホテル
    • Year and Date
      2010-08-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] 筋萎縮と筋肥大の分子機構を巡ってMolecular mechanisms of muscle atrophy and hypertrophy2010

    • Author(s)
      武田伸一
    • Organizer
      第3回上肢の神経機能回復セミナー
    • Place of Presentation
      秋田
    • Year and Date
      2010-05-14
    • Related Report
      2011 Final Research Report
  • [Presentation] 筋萎縮と筋肥大の分子機構を巡ってMolecular mechanisms of muscleatrophy and hypertrophy.2010

    • Author(s)
      武田伸一
    • Organizer
      第3回上肢の神経機能回復セミナー
    • Place of Presentation
      秋田角館広域交流センター
    • Year and Date
      2010-05-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Neuronal nitric oxide synthase is an essential mediator for muscle hypertrophy2009

    • Author(s)
      I to N, Ampong BN, Kudo A, Miyagoe-Suzuki Y, Takeda S
    • Organizer
      International Congress of Physiological Sciences
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-07-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Neuronal nitric oxide synthase is an essential mediator for muscle hypertrophy2009

    • Author(s)
      Ito N, Ampong BN, Kudo A, Miyagoe-Suzuki Y, Takeda S
    • Organizer
      International Congress of Physiological Sciences
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2009-07-29
    • Related Report
      2009 Annual Research Report
  • [Book] Mechanobiology in skeletal muscle : conversion of mechanical information into molecular signal. Mechanosensing Biology2010

    • Author(s)
      Miyagoe-Suzuki Y, Takeda S
    • Publisher
      Springer Japan
    • Related Report
      2011 Final Research Report
  • [Book] Mechanosensing Biology(ed.Masaki Noda)2010

    • Author(s)
      Miyagoe-Suzuki Y, Takeda S
    • Total Pages
      219
    • Publisher
      Springer Japan
    • Related Report
      2010 Annual Research Report
  • [Book] 骨格筋.炎症・再生医学事典2009

    • Author(s)
      鈴木友子,武田伸一
    • Publisher
      朝倉書店
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 筋増加剤及び筋増加物質のスクリーニング法2012

    • Inventor(s)
      武田伸一,伊藤尚基, Urs T. Ruegg,鈴木友子
    • Industrial Property Rights Holder
      NCNP
    • Industrial Property Number
      2012-063182
    • Filing Date
      2012-03-21
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 筋増加剤及び筋増加物質のスクリーニング法2012

    • Inventor(s)
      武田伸一, 伊藤尚基, Urs T.Ruegg, 鈴木友子
    • Industrial Property Rights Holder
      NCNP
    • Industrial Property Number
      2012-063182
    • Filing Date
      2012-03-21
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 筋肥大を促進する物質又は因子のスクリーニング法2011

    • Inventor(s)
      武田伸一,伊藤尚基, Urs T. Ruegg,鈴木友子
    • Industrial Property Rights Holder
      NCNP
    • Industrial Property Number
      2011-200716
    • Filing Date
      2011-09-24
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 筋肥大を促進する物質又は因子のスクリーニング法2011

    • Inventor(s)
      武田伸一, 伊藤尚基, Urs T.Ruegg, 鈴木友子
    • Industrial Property Rights Holder
      NCNP
    • Industrial Property Number
      2011-200716
    • Filing Date
      2011-09-24
    • Related Report
      2011 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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