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2011 Fiscal Year Research-status Report

ガンに伴う悪液質に対する低強度・高強度運動の萎縮予防効果の検証

Research Project

Project/Area Number 23650324
Research InstitutionKobe University

Principal Investigator

藤野 英己  神戸大学, 保健学研究科, 教授 (20278998)

Co-Investigator(Kenkyū-buntansha) 石原 昭彦  京都大学, 人間・環境学研究科(研究院), 教授 (90184548)
近藤 浩代  名古屋女子大学, 家政学部, 講師 (50333183)
村上 慎一郎  姫路獨協大学, 医療保健学部, 講師 (30454763)
Project Period (FY) 2011-04-28 – 2013-03-31
Keywordsリハビリテーション / 悪液質 / サイトカイン / 筋特異的リガーゼ
Research Abstract

本研究では、ガンによる悪液質を予防するための至適運動の開発、その運動効果と作用機序を解明することが目的である。特に運動による炎症性サイトカイン(腫瘍壊死因子(TNF-α)、IL-6)の変化に焦点をあて、ガンで誘導される因子、骨格筋萎縮の調節因子(筋特異的ユビキチンプロテアソーム系)、その他、レギュレータとなる主要因子を分子生物学的に解析し、ガンの悪液質に対する運動療法の効果を検証する。本年度は、筋萎縮に対する運動の効果検証する実験を行い、TNF-αやIL-6の変化について検証を行った。同時に悪液質のモデルとして、リポ多糖(LPS)を用いたモデルで運動の効果の検証や、Colon-26 Adenocarcinoma 細胞移植のための細胞培養を行った。特に筋萎縮に対する運動がTNF-αの減少を誘導し、プロテアソームのレギュレータとなる骨格筋特異的リガーゼAtrogin-1の低下も観察された。この研究の成果については、国際英文紙に投稿を行った。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

筋萎縮における炎症性サイトカインのTNF-αが、筋萎縮のリガンドとなり、筋特異的リガーゼのAtrogin-1活性を上昇させることを検証し、運動がTNF-αを低下させ、Atrogin-1活性を抑制した結果を得た。この結果から、運動がTNF-αを抑制することが検証できたため、リポ多糖(LPS)で悪液質を誘導して、運動がTNF-αを抑制することが可能かを検証した。また、Colon-26 Adenocarcinoma 細胞の移植によるガンモデルを作成する準備を行った。全体的に計画より少し遅れているが、確実に成果が出ていると考えられる。

Strategy for Future Research Activity

運動による効果が検証できているため、特にLPSによる悪液質誘導モデルやColon-26 Adenocarcinoma 細胞の移植によるガンモデルによる実験を中心に行っていく。また、共同研究者及び大学院生の連携体制も整っているために、共同研究者及び大学院生の協同により研究を推進していく。

Expenditure Plans for the Next FY Research Funding

LPSによる悪液質誘導モデルやColon-26 Adenocarcinoma 細胞の移植によるガンモデルの作成、バイオマーカーとして、TNF-α、Atrogin-1等の因子の分析を中心に研究費を使用する。また、得られた結果を公表するための発表費として使用する。

  • Research Products

    (22 results)

All 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (13 results)

  • [Journal Article] High-fat diet-induced reduction of peroxisome proliferator-activated receptorγ coactivator-1α messenger RNA levels and oxidative capacity in the soleus muscle of rats with metabolic syndrome.2012

    • Author(s)
      Nagatomo F, Fujino H, Kondo H, Takeda I, Tsuda K, Ishihara A.
    • Journal Title

      Nutr Res

      Volume: 32 Pages: 144-151

    • Peer Reviewed
  • [Journal Article] Differences in capillary architecture, hemodynamics, and angiogenic factors in rat slow and fast plantarflexor muscles.2012

    • Author(s)
      Fujino H, Kondo H, Murakami S, Nagatomo F, Fujita N, Takeda I, Ishihara A, Roy RR.
    • Journal Title

      Muscle Nerve

      Volume: 45 Pages: 242-249

    • DOI

      10.1002/mus.22267

    • Peer Reviewed
  • [Journal Article] The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.2012

    • Author(s)
      Nagatomo F, Fujino H, Kondo H, Kouzaki M, Gu N, Takeda I, Tsuda K, Ishihara A.
    • Journal Title

      J Physiol Sci

      Volume: 62 Pages: 105-114

    • Peer Reviewed
  • [Journal Article] A threshold dose of heavy ion radiation that decreases the oxidative enzyme activity of spinal motoneurons in rats.2012

    • Author(s)
      Ishihara A, Nagatomo F, Fujino H, Kondo H, Nojima K
    • Journal Title

      Neurochemical Research

      Volume: 37 Pages: 387-393

    • DOI

      10.1186/1743-7075-8-77

    • Peer Reviewed
  • [Journal Article] Regressed three-dimensional capillary network and inhibited angiogenic factors in the soleus muscle of non-obese rats with type 2 diabetes2011

    • Author(s)
      Kondo H, Fujino H, Murakami S, Nagatomo F, Roy RR, Ishihara A.
    • Journal Title

      Nutr Metab

      Volume: 8 Pages: 77

    • DOI

      10.1186/1743-7075-8-77

    • Peer Reviewed
  • [Journal Article] The combined effect of electrical stimulation and high-load isometric contraction on protein degradation pathways in muscle atrophy induced by hindlimb unloading2011

    • Author(s)
      Fujita N, Murakami S, Fujino H
    • Journal Title

      J Biomed Biotechnol

      Volume: 2011 Pages: 401493

    • DOI

      10.1155/2011/401493

    • Peer Reviewed
  • [Journal Article] PGC-1αand FOXO1 mRNA levels and fiber charactoristics of the soleus and plantaris muscles in rats after hindlimb unloading2011

    • Author(s)
      Nagatomo F, Fujino H, Kondo H, Suzuki H, Kouzaki M, Takeda I, Ishihara A
    • Journal Title

      Histol Histopathol

      Volume: 26 Pages: 1545-1553

    • Peer Reviewed
  • [Journal Article] PGC-1αmRNA level and oxidative capacity of the plantaris muscle in rats with metabolic syndrome, hypertension, and type 2 diabetes.2011

    • Author(s)
      Nagatomo F, Fujino H, Kondo H, Gu N, Takeda I, Ishioka N, Tsuda K, Ishihara A
    • Journal Title

      Acta Histochem Cytochem

      Volume: 28 Pages: 73-80

    • DOI

      10.1267/ahc.10041

    • Peer Reviewed
  • [Journal Article] The combined effect of electrical stimulation and resistance isometric contraction on muscle atrophy in rat tibialis anterior muscle2011

    • Author(s)
      Fujita N, Murakami S, Arakawa T, Miki A, Fujino H
    • Journal Title

      Bosn J Basic Med Sci

      Volume: 11 Pages: 1-6

    • Peer Reviewed
  • [Presentation] Exercise training prevents the microangiopathy of skeletal muscle in non-obese goto-kakizaki rats.2011

    • Author(s)
      Fujino H, Kondo H, Murakami S, Nagatomo F, Fujita N, Ishihara A
    • Organizer
      7th Federation of the Asian and Oceanian Physiological Societies Congress
    • Place of Presentation
      Taipei
    • Year and Date
      2011.9.11
  • [Presentation] Low-intensity exercise prevents hyperglycemia and hyperlipidemia in spontaneously type 2 diabetic torii rat2011

    • Author(s)
      Kondo H, Fujino H, Murakami S, Fujita N, Morifuji T, Shiina S, Nagatomo F, Ishihara A
    • Organizer
      7th Federation of the Asian and Oceanian Physiological Societies Congress
    • Place of Presentation
      Taipei
    • Year and Date
      2011.9.11
  • [Presentation] Thrapeutic exercise attenuates microangiopathy of skeletal muscle in type 2 diabetes.2011

    • Author(s)
      Fujino H, Murakami S, Kondo H, Fujita N, Nagatomo F, Takeda I, Ishihara A
    • Organizer
      World Confederation for Physical Therapy 2011
    • Place of Presentation
      Amsterdam
    • Year and Date
      2011.6.20
  • [Presentation] Protective effects of isometric contraction using electrical stimulation on muscle atrophy2011

    • Author(s)
      Fujita N, Fujino H
    • Organizer
      World Confederation for Physical Therapy 2011
    • Place of Presentation
      Amsterdam
    • Year and Date
      2011.6.20
  • [Presentation] Abnormality of myosin heavy chain isoform type and succinate dehydrogenase activity in soleus muscle of diabetec rat.2011

    • Author(s)
      Murakami S, Kondo H, Fujita N, Fujino H
    • Organizer
      World Confederation for Physical Therapy 2011
    • Place of Presentation
      Amsterdam
    • Year and Date
      2011.6.20
  • [Presentation] Benefical effect of nutritional support against regression of capillary network in atrophied slow muscle.2011

    • Author(s)
      Kanazashi M, Okumura Y, Fujita, Murakami S, Fujino H
    • Organizer
      World Confederation for Physical Therapy 2011
    • Place of Presentation
      Amsterdam
    • Year and Date
      2011.6.20
  • [Presentation] High-intensity exercise training attenuates diabetes-induced muscle capillary regression in non-obese NIDDM rats.2011

    • Author(s)
      Fujino H, Kondo H, Murakami S, Fujita N, Nagatomo F, Takeda I, Ishihara A, Roy RR.
    • Organizer
      58th American college of sports medicine
    • Place of Presentation
      Denver
    • Year and Date
      2011.5.31
  • [Presentation] Low-intensity exercise prevents hyperglycemia and hyperlipidemia in spontaneously type 2 diabetic torii rat.2011

    • Author(s)
      Kondo H, Fujino H, Murakami S, Fujita N, Morifuji T, Shiina S, Nagatomo F, Ishihara A.
    • Organizer
      58th American college of sports medicine
    • Place of Presentation
      Denver
    • Year and Date
      2011.5.31
  • [Presentation] Low-intensity exercise training prevents muscular microangiopathy in non-obese type 2 diabetic rats2011

    • Author(s)
      Fujino H, Kondo H, Murakami S, Fujita N, Morifuji T, Nagatomo F, Ishihara A
    • Organizer
      Experimental Biology 2011
    • Place of Presentation
      Washington DC
    • Year and Date
      2011.4.9
  • [Presentation] Effects of exercise preconditioning on capillary in soleus muscle of type 2 diabetic rats2011

    • Author(s)
      Murakami S, Morifuji T, Kondo H, Takeda I, Fujita N, Fujino H
    • Organizer
      Experimental Biology2011
    • Place of Presentation
      Washington DC
    • Year and Date
      2011.4.9
  • [Presentation] Estrogen receptor-alpha genotype affects exercise-related bone mass in young healthy women2011

    • Author(s)
      Kondo H, Fujino H, Murakami S, Fujita N, Nagatomo F, Ishihara A
    • Organizer
      Experimental Biology 2011
    • Place of Presentation
      Washington DC
    • Year and Date
      2011.4.9
  • [Presentation] Three-dimensional visualization of capillary and prevention of capillary regression by antioxidant supplementation in disused skeletal muscle2011

    • Author(s)
      Fujino H, Kanazashi M, Kondo H, Murakami S, Nagatomo F, Fujita N, Ishihara A
    • Organizer
      51th annual meeting of American society for cell biology
    • Place of Presentation
      Denver
    • Year and Date
      2011.12.3
  • [Presentation] Three-dimensional microcirculatory measurements and the protective effects of endurance exercise on its complications in non-obese type 2 diabetic muscle.2011

    • Author(s)
      Kondo H, Fujino H, Murakami S, Nagatomo F, Fujita N, Ishihara A.
    • Organizer
      51th annual meeting of American society for cell biology
    • Place of Presentation
      Denver
    • Year and Date
      2011.12.3

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Published: 2013-07-10  

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