• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pathomechanism of distal myopathy with rimmed vacuoles and GNE gene aberration

Research Project

Project/Area Number 15590898
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOita University (2004-2005)
大分医科大学 (2003)

Principal Investigator

KUMAMOTO Toshihide  Oita University, Faculty of Medicine, Department of Brain and Nerve Science (Internal Medicine 3), M.D., Professor, 医学部, 教授 (40134936)

Co-Investigator(Kenkyū-buntansha) UEYAMA Hidetsugu  Oita University, Faculty of Medicine, Department of Brain and Nerve Science (Internal Medicine 3), M.D., Assistant Professor, 医学部, 講師 (20281214)
ARAKAWA Ryuki  Oita University, Faculty of Medicine, Department of Brain and Nerve Science (Internal Medicine 3), M.D., Assistant Professor, 医学部, 助手 (90363548)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsdistal myopathy / chloroquine-induced myopathy / inclusion body myositis / rimmed vacuoles / GNE / anti-GNE antibody / mutant GNE cell / lysosome system / モデル細胞 / ubiquitin / proteasome / MuRF-1 / Atrogin-1 / lysosome / M6PR / 細胞モデル / SiRNA法 / lysosome system / 遺伝子組み換え蛋白 / Apg遺伝子
Research Abstract

To understand the pathomechanism and development of the therapy for distal myopathy with rimmed vacuoles (DMRV), we studied on the role of lysosomal system in the muscle fiber destruction of various human and animal rimmed vacuolar myopathies, localization of GNE in mammalian tissues and cells, and preparation of mutant GNE cells and GNE knock-down cells.
In solitary inclusion body myositis (IBM), showing numerous rimmed vacuoles in muscle fibers, abnormal increases in the lysosome- related proteins and genes, especially receptor mediated intracellular transport-related proteins such as mannose 6-phosphate receptor (M6PR) and clathrin, and autophagy-related genes such as hAtg5 and hAtg12, were demonstrated in IBM muscles as compared with normal and diseased controls. We also measured the expression levels of protein and/or mRNA for lysosome-related proteins in the denervated and innervated soleus muscles from saline- and chloroquine-treated rats using the Northern blot. The denervated m … More uscle of chloroquine-treated rats is known as animal model of human DMRV. Accumulation of vacuoles was observed only in chloroquine-treated denervated muscles. Further, clathrin immunostaining and M6PR mRNA were significantly increased in denervated soleus muscle from saline and chloroquine-treated rats compared to contralateral, innervated muscles. These data suggest that the transport of newly synthesized lysosomal enzymes from the secretory pathway via the trans-Golgi network of the Golgi apparatus (an endosomal pathway) as well as autophagosome formation (an autophagic process) were activated in the skeletal muscles of various rimmed vacuolar myopathy such as IBM and chloroquine-induced myopathy. Vacuoles may subsequently accumulate secondary to abnormal formation or turnover of autolysosomes at or after fusion of autophagosomes with early endosomes.
Two polyclonal UDP-N-acetylglucosamine-2-epimerase/ N-acetylmannosamine kinase (GNE) antisera were raised in rabbit against recombinant GNE proteins. Western blots, a single protein band of about 79 kDa is detected in crude extracts of culture cells such as HEK293, and various mammalian tissues and cells. Our immunohistochemistry and Western blots demonstrated ubiquitously expression in all tissues and cells including muscle. The expression level of GNE was high in liver, whereas it was low in muscles. The immunofluorescence study showed strongly positive granular reaction for GNE in the cytoplasm and nucleus.
Furthermore, we prepared the myotube cells with mutant GNE protein (V572L). We are studying the difference in the pathology and function between both mutant GNE cell and wild-type cell. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2006 2005 2004 Other

All Journal Article (16 results) Publications (1 results)

  • [Journal Article] Striated muscle fiber compositions of human male urethral rhabdosphincter and levator ani.2006

    • Author(s)
      Sumino Y, Sato F, Kumamoto T, Mimata H.
    • Journal Title

      J Urol 175(4)

      Pages: 1417-1421

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Skeletal muscle expression of clathrin and mannose 6-phosphate receptor in experimental chloroquine-induced myopathy.2005

    • Author(s)
      Masuda T, Ueyama H, Nakamura K, Jikumaru M, Toyoshima I, Kumamoto T.
    • Journal Title

      Muscle Nerve 31(4)

      Pages: 495-502

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Myosin loss in denervated rat soleus muscle after dexamethasone treatment.2005

    • Author(s)
      Horinouchi H, Kumamoto T, Kimura N, Ueyama H, Tsuda T.
    • Journal Title

      Pathobiology 72(3)

      Pages: 108-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Skeletal muscle expression of clathrin and mannose 6-phosphate receptor in experimental chloroquine-induced myopathy.2005

    • Author(s)
      Masuda T, Ueyama H, Nakamura K, Jikumaru M, Toyoshima I, Kumamoto T
    • Journal Title

      Muscle Nerve 31

      Pages: 495-502

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Myosin loss in denervated rat soleus muscle after dexamethasone treatment.2005

    • Author(s)
      Horinouchi H, Kumamoto T, Kimura N, Ueyama H, Tsuda T
    • Journal Title

      Pathobiology 72

      Pages: 108-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early assessment of rapidly progressive interstitial pneumonia associated with amyopathic dermatomyositis.2005

    • Author(s)
      Miyazaki E, Ando M, Muramatsu T, Fukumi T, Matsuno O, Nureki SI, Ueno T, Tsuda T, Kumamoto T.
    • Journal Title

      Clin Rheumatol 20(Epub ahead of print)

      Pages: 1-4

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Progressive multifocal leukoencephalopathy in an HTLV-I carrier.2005

    • Author(s)
      Kimura A, Ueyama H, Kimura N, Fujimoto S, Kumamoto T.
    • Journal Title

      Clin Neurol Neurosurg 26(Epub ahead of print)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Myosin loss in denervated rat soleus muscle after dexamethasone treatment.2005

    • Author(s)
      Horiuchi H, Kumamoto T, Kimura N, Ueyama H, Tsuda T.
    • Journal Title

      Pathobiology 72(3)

      Pages: 108-116

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Distal myopathy with rimmed vacuoles(DMRV)をめぐって2005

    • Author(s)
      熊本俊秀
    • Journal Title

      熊本大学神経内科同門会誌 9

      Pages: 15-28

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of lysosome-related proteins and genes in the skeletal muscles of inclusion body myositis.2004

    • Author(s)
      Kumamoto T, Ueyama H, Tsumura H, Toyoshima I, Tsuda T
    • Journal Title

      Acta Neuropathol (Berl) 107(1)

      Pages: 59-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rimmed vacuolesを伴う遠位型ミオパチーの病態と治療への展望。2004

    • Author(s)
      熊本俊秀
    • Journal Title

      神経治療 21(5)

      Pages: 537-543

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of lysosome-related proteins and genes in the skeletal muscles of inclusion body myositis.2004

    • Author(s)
      Kumamoto T, Ueyama H, Tsumura H, Toyoshima I, Tsuda T
    • Journal Title

      Acta Neuropathol (Berl) 107

      Pages: 59-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A view of pathogenesis and treatment of distal myopathy with rimmed vacuoles.2004

    • Author(s)
      Kumamoto T
    • Journal Title

      Neurological Therapeutics 21

      Pages: 537-543

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A case of diffuse panbronchiolitis (DPB) in a patient positive for HTLV-1.2004

    • Author(s)
      Matsuno O, Watanabe K, Kataoka H, Miyazaki E, Kumamoto T.
    • Journal Title

      Scand J Infect Dis 36(9)

      Pages: 687-689

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rimmed vacuolesを伴う遠位型ミオパチーの病態と治療への展望2004

    • Author(s)
      熊本俊秀
    • Journal Title

      神経治療 21(5)

      Pages: 537-543

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Myosin loss in denervated rat soleus muscle after dexamethasone treatment.

    • Author(s)
      Horinouchi H, Kumamoto T, Kimura N, Ueyama H, Tsuda T.
    • Journal Title

      Pathobiology (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Kumamoto Toshihide: "Expression of lysosome-related proteins and genes in the skeletal muscles of inclusion body myositis"Acta Neuropathologica (Berl). 107(1). 59-65 (2004)

    • Related Report
      2003 Annual Research Report

URL: 

Published: 2003-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi