Molecular meohanisms of mechanosensing inskeletal muscles : Based on regulation system of atrogen expression

• Project/Area Number: 19500564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Sports science
• Research Institution: The University of Tokushima
• Principal Investigator: NIKAWA Takeshi The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (20263824)
• Co-Investigator(Kenkyū-buntansha): YASUI Matsuo 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (00157984) ; NAKAYA Yutaka 徳島大学, 大学院・ヘルスバシオサイエンス研究部, 教授 (50136222)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ユビキチンリガーゼ / 機械的ストレスの感知 / IGF-1シグナル / 運動器(筋・骨) / 蛋白質分解酵素

Research Abstract

Cb1-bの発現が運動器の活動状態(機械的ストレス)と相関する非常に良い指標になることがわかった。この新しい知見は、Cb1-bの発現調節機序を解明できれば機械的ストレスに対する運動器の感知機構が明らかになることを強く示唆した。そこで、本研究で、Cb1-b遺伝子のプロモーター解析を行った結果、Egr-1とSp1の転写因子がCb1-bの発現をそれぞれ正と負に制御していることがわかった。さらに、これら転写因子の上流を解析すると、MAPK経路とくにERK-1/2経路がEgrの活性を誘導していた。ERK-1/2を活性化するものこそが、運動器の活動状態(機械的ストレス)の感知機構の重要なセンサーであることがほぼ明らかにした。申請者らは、それが膜上の蛋白質分解酵素ではないかという新たなメカニズムを提唱している。

Research Products

• [Journal Article] Awa(Tokushima)lactate-fermented tea as well as green tea enhance the effect of diet restriction on obesity in rats (2009)
  • Author(s): Sogawa M, Seura T, Kohno S, Hirasaka K, Yamaguchi Y, Takagi R, Harada A, Okumura Y, Yamamoto S, Kishi K, Nikawa T
  • Journal Title: J Med Invest 56(1-2) Pages: 42-48
  • NAID: 130004465165
  • Peer Reviewed
• [Journal Article] Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes (2009)
  • Author(s): Hemdan DII, Hirasaka K, Nakao R, Kohno S, Kagawa S, Abe T, Harada-Sukeno A, Okumura Y, Nakaya Y, Terao J, Nikawa T
  • Journal Title: J Med Invest 56(1-2) Pages: 26-32
  • NAID: 130004465163
  • Peer Reviewed
• [Journal Article] Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats (2009)
  • Author(s): Mikura M, Yamaoka I, Doi M, Kawano Y, Nakayama M, Nakao R, Hirasaka K, Okumura Y, Nikawa T
  • Journal Title: Anesthesiology 110(1) Pages: 81-8
  • Peer Reviewed
• [Journal Article] Awa (Tokushima) lactate-fermented tea as well as green tea enhance the effect of diet restriction on obesity in rats (2009)
  • Author(s): Sogawa M, et al.
  • Journal Title: J Med Invest 56(1-2) Pages: 42-48
  • Peer Reviewed
• [Journal Article] Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes (2009)
  • Author(s): Hemdan DII, et al.
  • Journal Title: J Med Invest 56(1-2) Pages: 26-32
  • Peer Reviewed
• [Journal Article] Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats (2009)
  • Author(s): Mikura M, et al.
  • Journal Title: Anesthesiology 110(1) Pages: 81-88
  • Peer Reviewed
• [Journal Article] Peroxidized cholesterol-induced matrix metalloproteinase-9 activation and its suppression by dietary beta-carotene in photoaging of hairless mouse skin (2009)
  • Author(s): Minami Y, et al.
  • Journal Title: J Nutr Biochem 23(in press)
  • Peer Reviewed
• [Journal Article] Effects of Dimethyl Sulphoxide and Dexamethasone on mRNA Expression of Myogenesis- and Muscle Proteolytic System-related Genes in Mouse Myoblastic C2C12 Cells (2008)
  • Author(s): Nishimura M, Mikura M, Hirasaka K, Okumura Y, Nikawa T, Kawano Y, Nakayama M, Ikeda M
  • Journal Title: J Biochem 144(6) Pages: 717-724
  • NAID: 10024913840
  • Peer Reviewed
• [Journal Article] athepsin C propeptide interacts with intestinal alkaline phosphatase and heat shock cognate protein 70 in human Caco-2 cells (2008)
  • Author(s): Hirasaka K, Tokuoka K, Nakao R, Yamada C, Oarada M, Imagawa T, Ishidoh K, Okumura Y, Kishi K, Nikawa T
  • Journal Title: Physiol Sci 58(2) Pages: 105-11
  • 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, Hirasaka K, Goto J, Nikawa T, Shono M, Yoshida M, Stoward PJ
  • Journal Title: Histochem Cell Biol 129(4) Pages: 489-501
  • 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, Tsuzuki T, Gonoi T, Igarashi H, Kamei K, Nikawa T, Hirasaka K, Ogawa T, Miyazawa T, Nakagawa K, Kurita N
  • Journal Title: Nutrition 24(1) Pages: 67-75
  • Peer Reviewed
• [Journal Article] Effects of Dimethy1 Sulfoxide and Dexamethasone on mRNA Expression of Housekeeping Genes in Cultures of C2C12 Myotubes (2008)
  • Author(s): Masuhiro Nishimura M, Nikawa T, Kawano Y, Nakayama M, Muneharu Ikeda M
  • Journal Title: Biochem Biophys Res Commun 367(3) Pages: 603-8
  • 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, Tsuzuki T, Gonoi T, Igarashi H, Kamei K, Nikawa T, Hirasaka K, Ogawa T, Miyazawa T, Nakagawa K, Kurita N
  • Journal Title: Nutrition 24 (1) Pages: 67-75
  • Peer Reviewed
• [Journal Article] Peroxidized cholesterol-induced matrix metalloproteinase-9 activation and its suppression by dietary beta-carotene in photoaging of hairless mouse skin (2008)
  • Author(s): Minami Y, Kawabata K, Kubo Y, Arase S, Hirasaka K, Nikawa T, Banda N, Kawai Y, Terao J
  • Journal Title: J Nutr Biochem 23
  • Peer Reviewed
• [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 58(2) Pages: 105-111
  • 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
  • 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 Bid 129 Pages: 489-501
  • Peer Reviewed
• [Journal Article] Effects of dimethyl sulphoxide and dexamethasone on mRNA expression of myogenesis- and muscle proteolytic system-related genes in mouse myoblastic C2C12 cells (2008)
  • Author(s): Nishimura M, et al.
  • Journal Title: J Biochem (Tokyo) 144(6) Pages: 714-724
  • Peer Reviewed
• [Journal Article] Preventive effect of isometric contraction exercise on disuse muscle atrophy using tail suspension mice (2008)
  • Author(s): Kawahara Y, et al.
  • Journal Title: J. Phys. Ther. Sci 20 Pages: 39-44
  • Peer Reviewed
• [Journal Article] Effects of dimethyl sulfoxide and dexamethasone on mRNA expression of housekeeping genes in cultures of C2C12 myotubes (2008)
  • Author(s): Nishimura M, et al.
  • Journal Title: Biochem Biophys Res Commun 367(3) Pages: 603-608
  • Peer Reviewed
• [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)
  • 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
  • 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
  • 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, Tamura S, Mameoka M, Yamada C, Ogawa T, Hirasaka K, Okumura Y, Imagawa T, Oguri S, Ishidoh K, Kishi K, Higashiyama S, Nikawa T
  • Journal Title: FEBS Lett 581(30) Pages: 5743-50
  • Peer Reviewed
• [Journal Article] Deficiency of Cb1-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice (2007)
  • Author(s): Hirasaka K, Kohno S, Goto J, Furochi H, Mawatari K, Hamada N, Hosaka T, Nakaya Y, Ishidoh K, Obata T, Ebina Y, Gu H, Takeda S, Kishi K, Nikawa T
  • Journal Title: Diabetes 56(10) Pages: 2511-22
  • Peer Reviewed
• [Journal Article] istinct effects of anterior pyriform cortex and the lateral hypothalamus lesions on protein intake in rats (2007)
  • Author(s): Nakao R, Ozaki E, Hasegawa M, Kondo A, Uezu K, Hirasaka K, Nikawa T, Kishi K
  • Journal Title: J Med Invest 54(3-4) Pages: 255-60
  • Peer Reviewed
• [Journal Article] Overexpression of osteoactivin protects skeletal muscle from severe degeneration caused by long-term denervation in mice (2007)
  • Author(s): urochi H, Tamura S, Takeshima K, Hirasaka K, Nakao R, Kishi K, Nikawa T
  • Journal Title: J Med Invest 54(3-4) Pages: 248-54
  • NAID: 130004822546
  • Peer Reviewed
• [Journal Article] (2007)
  • Author(s): Nakano S, Mishiro T, Takahara S, Yokoi H, Hamada D, Yukata K, Takata Y, Goto T, Egawa H, Yasuoka S, Furouchi H, Hirasaka K, Nikawa T, Yasui N. Nakano S, Mishiro T, Takahara S, Yokoi H, Hamada D, Yukata K, Takata Y, Goto T, Egawa H, Yasuoka S, Furouchi H, Hirasaka K, Nikawa T, Yasui N
  • Journal Title: Clin Rheumatol 26(8) Pages: 1284-92
  • Peer Reviewed
• [Journal Article] Effects of single administration of Rokumi-gan (TJ-87) on serum amino acid concentration of 6 healthy Japanese male volunteers (2007)
  • Author(s): akahashi H, Nakao R, Hirasaka K, Kishi K, Nikawa T
  • Journal Title: J Med Invest 54(1-2) Pages: 91-8
  • NAID: 120006470118
  • Peer Reviewed
• [Journal Article] Effect of dietary oils on lymphocyte immunological activity in psychologically stressed mice (2007)
  • Author(s): Oarada M, Gonoi T, Tsuzuki T, Igarashi M, Hirasaka K, Nikawa T, Onishi Y, Toyotome T, Kamei K, Miyazawa T, Nakagawa K, Kashima M, Kurita N
  • Journal Title: iosci Biotechnol Biochem 71(1) Pages: 174-82
  • NAID: 10027510395
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Sensing mechanism of unloading stress in skeletal muscle cells (2008)
  • Author(s): 二川健
  • Organizer: 第4回日韓宇宙フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02
• [Presentation] Development of a functional food or drug against unloading-mediated muscle atrophy (2008)
  • Author(s): 二川健
  • Organizer: 37th COSPAR Scientific Assembly
  • Place of Presentation: モントリオール・カナダ
• [Presentation] Unloadingによる筋萎縮の主要な制御因子 (2007)
  • Author(s): 二川健
  • Organizer: Unloadingによる筋萎縮の主要な制御因子
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Unloadingによる筋萎縮の主要な制御因子 (2007)
  • Author(s): 二川 健
  • Organizer: 日本生化学会・分子生物学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] 宇宙における細胞培養実験の必要性と問題点 (2007)
  • Author(s): 二川健
  • Organizer: 第13回宇宙医学研究推進分科会 : 宇宙基礎医学生物学研究に用いるべき最適なモデル生物に関するワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2007-12-11
• [Presentation] 宇宙における細胞培養実験の必要性と問題点 (2007)
  • Author(s): 二川 健
  • Organizer: 第13回宇宙医学研究推進分科会:宇宙基礎医学生物学研究に用いるべき最適なモデル生物に関するワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2007-12-11
• [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
• [Book] 運動器の生物学と生体力学各組織の力学特性と病態-骨格筋 (2008)
  • Author(s): 二川健、安井夏生(分担)
  • Total Pages: 500
  • Publisher: 中山書店最新整形外科学大系
• [Book] 運動器の生物学と生体力学筋・腱-構造と筋収縮の生理学 (2008)
  • Author(s): 松浦哲也、二川健(分担)
  • Total Pages: 500
  • Publisher: 中山書店最新整形外科学大系
• [Book] 最新整形外科学大系(1)運動器の生物学と生体力学筋・腱-構造と筋収縮の生理学 (2008)
  • Author(s): 松浦哲也, 二川 健(分担)
  • Total Pages: 500
  • Publisher: 中山書店
• [Book] 最新整形外科学大系(1)運動器の生物学と生体力学各組織の力学特性と病態-骨格筋 (2008)
  • Author(s): 二川 健, 安井夏生(分担)
  • Total Pages: 500
  • Publisher: 中山書店
• [Book] 栄養・食糧学用語辞典 (2007)
  • Author(s): 二川健(分担)
  • Publisher: 建吊社
• [Book] 栄養・食糧学会語辞典 (2007)
  • Author(s): 二川 健(分担)
  • Publisher: 建帛社
• [Remarks]
  • URL: http://150.59.76.31/university/servlet/index/index?&level=4&reference=0/10002/5/30010/20032