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Development of oligopeptides against skeletal muscle fatigue and atrophy caused by unloading

Research Project

Project/Area Number 18590218
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionThe University of Tokushima

Principal Investigator

OGURI Sachiko (2007)  The University of Tokushima, Institute of Health Biosciences, Graduate School, Technician (50380085)

岸 恭一 (2006)  徳島大学, 大学院ヘルスバイオサイエンス研究科, 教授 (80035435)

Co-Investigator(Kenkyū-buntansha) NIKAWA Takeshi  The University of Tokushima, Institute of Health Biosciences, Graduate School, Professor (20263824)
YASUI Natsuo  The University of Tokushima, Institute of Health Biosciences, Graduate School, Professor (00157984)
NEMOTO Hisao  The University of Tokushima, Institute of Health Biosciences, Graduate School, Associate Professor (30208293)
KISHI Kyoichi  Nagoya University of Arts and Sciences, Department of Nutritional Sciences, Professor (80035435)
大栗 幸子  徳島大学, 大学院ヘルスバイオサイエンス研究科, 技術職員 (50380085)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsdenervation / oligopeptides / IGF-1 signaling / ubiquitin ligase / unloading-mediated muscle atrophy / anti-aging diet / ユビチキン化阻害剤 / 筋萎縮 / ユビチキンリガーゼ / オリゴペプチド大量発現法
Research Abstract

Skeletal muscle unloading during prolonged bed rest, paralysis, and spaceflight results in mechanical stress that can lead to debilitating atrophy. This atrophic response is characterized by both decreased responsiveness to myogenic growth factors IGF-1/insulin and increased proteolysis. Here we show that unloading stress activated a redox-dependent atrophic signaling pathway that ultimately led to the induction of the ubiquitin ligase Cbl-b downstream of Egr transcription factors. Upon induction, Cbl-b interacted with and degraded the IGF-1 signaling intermediate IRS-1, leading to FOXO3-dependent induction of atrogin-1, a dominant mediator of proteolysis in atrophic muscle. Cbl-b expression alone was sufficient to induce IRS-1 ubiquitination and atrophy in rat tibialis anterior muscle. In contrast, Cbl-b-deficient mice were resistant to unloading-induced atrophy, weakness (tetanic force), and loss of coordination. Furthermore, a penta-peptide mimetic of tyrosine^<612>-phosphorylated IRS-1 inhibited Cbl-b-mediated IRS-1 ubiquitination and strongly decreased Cbl-b-mediated induction of atrogin-1. Our results indicate that the Cbl-b-dependent destruction of IRS-1 is a critical dual mediator of both the growth refractory and proteolytic arms of the atrophic response. Inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (39 results)

All 2008 2007 2006

All Journal Article (32 results) (of which Peer Reviewed: 16 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Cathepsin C propeptide interacts with intestinal alkaline phosphatase and heat shock cognate protein 70 in human Caco-2 cells.2008

    • Author(s)
      Hirasaka K, et. al.
    • Journal Title

      J Phys Sci (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of dietary fish oil on lipid peroxidation and serum triacylglycerol levels in psychologically stressed mice.2008

    • Author(s)
      Oarada M, et. al.
    • Journal Title

      Nutrition 24

      Pages: 67-75

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study.2008

    • Author(s)
      Nakae Y., et. al.
    • Journal Title

      Histochem Cell Biol 129

      Pages: 489-501

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cathepsin C propeptide interacts with intestinal alkaline phosphatase and heat shock cognate protein 70 in human Caco-2 cells2008

    • Author(s)
      Hirasaka, K, et. al.
    • Journal Title

      J Phys Sci (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of dietary fish oil on lipid peroxidation and serum triacylglycerol levels in psychologically stressed mice2008

    • Author(s)
      Oarada, M, et. al.
    • Journal Title

      Nutrition 24(1)

      Pages: 67-75

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice : a quantitative histological, immunohistochemical and electrophysiological study2008

    • Author(s)
      Nakae, Y, et. al.
    • Journal Title

      Histochem Cell Biol 129(4)

      Pages: 489-501

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cathepsin C propeptide interacts with intestinal alkaline phosphatase and heat shock cognate protein 70 in human Caco-2 cells.2008

    • Author(s)
      Hirasaka K, et. al.
    • Journal Title

      J Phys Sci

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of dietary fish oil on lipid peroxidation and serum triacylglycerollevels in psychologically stressed mice.2008

    • Author(s)
      Oarada M, et. al.
    • Journal Title

      Nutrition 24

      Pages: 67-75

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subcutaneous injection,from birth,of epigallocatechin-3-gallate,a component of green tea,limits the onset of muscular dystrophy in mdx mice:a quantitative histological,immunohistochemical and electrophysiological study.2008

    • Author(s)
      Nakae Y, et. al.
    • Journal Title

      Histochem Cell Biol 129

      Pages: 489-501

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice.2007

    • Author(s)
      Hirasaka K, et. al.
    • Journal Title

      Diabetes 56

      Pages: 2511-2522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis.2007

    • Author(s)
      Nakano S, et. al.
    • Journal Title

      Clin Rheumatol 26

      Pages: 1284-1292

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effect of dietary oils on lymphocyte immunological activity in psychologically stressed mice.2007

    • Author(s)
      Oarada M, et. al.
    • Journal Title

      Biosci Biotechnol Biochem 71

      Pages: 174-182

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of single administration of Rokumi-gan (TJ-87) on serum aminoacid concentration of 6 healthy Japanese male volunteers.2007

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

      J Med Invest 54

      Pages: 91-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Overexpression of osteoactivin protects skeletal muscle from severe degeneration caused by long-term denervation in mice.2007

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

      J Med Invest 54

      Pages: 248-254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Distinct effects of the lateral hypothalamus and anterior pyriform cortex destructions on protein intake in rats.2007

    • Author(s)
      Nakao R, et. al.
    • Journal Title

      J Med Invest 54

      Pages: 255-260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts.2007

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

      FEBS Lett 581

      Pages: 5743-5750

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice2007

    • Author(s)
      Hirasaka, K, et. al.
    • Journal Title

      Diabetes 56(10)

      Pages: 2511-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis2007

    • Author(s)
      Nakano, S, et. al.
    • Journal Title

      Clin Rheumatol 26(8)

      Pages: 1284-92

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of dietary oils on lymphocyte immunological activity in psychologically stressed mice2007

    • Author(s)
      Oarada, M, et. al.
    • Journal Title

      Biosci Biotechnol Biochem 71(1)

      Pages: 174-82

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of single administration of Rokumi-gan(TJ-87)on serum amino acid concentration of 6 healthy Japanese male volunteers2007

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

      J Med Invest 540

      Pages: 91-98

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Overexpression of osteoactivin protects skeletal muscle from severe degeneration caused by long-term denervation in mice2007

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

      J Med Invest 540

      Pages: 248-254

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distinct effects of the lateral hypothalamus and anterior pyriform cortex destructions on protein intake in rats2007

    • Author(s)
      Nakao, R, et. al.
    • Journal Title

      J Med Invest 540

      Pages: 255-260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts2007

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

      EBBS Lett 5810

      Pages: 5743-5750

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distinct expression of mast cell tryptase and protease activated receptor-2in synovia of rheumatoid arthritis and osteoarthritis.2007

    • Author(s)
      Nakano S, et. al.
    • Journal Title

      Clin Rheumatol 26

      Pages: 1284-1292

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of single administration of Rokumi-gan(TJ-87)on serum aminoacid concentration of 6 healthy Japanese male volunteers.2007

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

      J Med Invest 54

      Pages: 91-98

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct effects of the lateral hypothalamus and anterior pyriform tortex destructions on protein intake in rats.2007

    • Author(s)
      Nakao R, et. al.
    • Journal Title

      J Med Invest 54

      Pages: 255-260

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Shingle Administration of Rokumi-gan(TJ-87) on Serum Amino Acid Concentration of 6 Healthy Japanese Male Volunteers.2007

    • Author(s)
      Takahashi H. et al.
    • Journal Title

      J Med Invest 54(1-2)

      Pages: 91-98

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct gene expression profiles in the femora of rats exposed to spaceflight, tailsuspension and denervation.2007

    • Author(s)
      Furochi H. et al.
    • Journal Title

      Biol Sci Space (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Overexpression of osteoactivin protects skeletal muscle from severe degeneration caused by long-term denervation in mice.2007

    • Author(s)
      Furochi H. et al.
    • Journal Title

      J Med Invest (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct effects of anterior pyriform cortex and the lateral hypothal amus lesion on protein intake in rats2007

    • Author(s)
      Nakao R. et al.
    • Journal Title

      J Med Invest (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Soy protein diet prevents hypermethioninemia caused by portacaval shunt in rats2006

    • Author(s)
      Shimooka R. et la.
    • Journal Title

      J Med Invest 53(3-4)

      Pages: 255-263

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A skeletal muscle-derived secretory protein, attractin, upregulates UCP-2 expression in mouse 3T3-L1 adipocytes.2006

    • Author(s)
      Nikawa T. et al.
    • Journal Title

      Biol Sci Space 20(2)

      Pages: 33-39

    • NAID

      10018709316

    • Related Report
      2006 Annual Research Report
  • [Presentation] Cbl-bを介したマクロファージ活性化制御機構2007

    • Author(s)
      加川 祥子, ら
    • Organizer
      日本栄養・食糧学会中四国支部会
    • Place of Presentation
      広島
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Cbl-b-mediated activation of macrophages2007

    • Author(s)
      Kagawa, S., et. al.
    • Organizer
      Annual Meeting of Japanese Society of Nutrition and Food Science, Shikoku-Chugoku Branch
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice2007

    • Author(s)
      Kohno S, et. al.
    • Organizer
      General Meeting of the International Proteolysis Society
    • Place of Presentation
      Patras, Greece
    • Year and Date
      2007-10-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Deficiency of Cbl-b gene enhances infiltration and activation of macrophagesin adipose tissue and causes peripheral insulin resistance in mice2007

    • Author(s)
      Kohno S, et. al.
    • Organizer
      General Meeting of the International Proteolysis Society
    • Place of Presentation
      Patras,Greece
    • Year and Date
      2007-10-23
    • Related Report
      2007 Annual Research Report
  • [Presentation] Cbl-b欠損によるマクロファージの活性化とインスリン抵抗性2007

    • Author(s)
      平坂 勝也
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      京都
    • Year and Date
      2007-05-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Macrophage activation and insulin resistance2007

    • Author(s)
      Hirasaka, K., et. al.
    • Organizer
      Annual Meeting of Japanese Society of Nutrition and Food Science
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2007-05-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] たんぱく質・アミノ酸の新栄養学2007

    • Author(s)
      岸 恭一, 木戸康博
    • Total Pages
      240
    • Publisher
      講談社サイエンティフィック
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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