Project/Area Number |
07670702
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
KOBAYASHI Tadayoshi Tokyo Medical and Dental University, Department of Neurology, Assistant professor, 医学部, 講師 (70115343)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | Myotonic dystrophy / myotonic dystrophy protein kinase / sarcoplasmic reticulum / trinucleatide repeat / skeletal muscle / cardiac muscle / immunohistochemistry / immunoelectron microscopy / 筋電張性ジストロフィー / 筋緊張性ジストロフィープロテインキナーゼ / ミオトニンプロテインキナーゼ / 体細胞分裂 / 神経支配 / 三塩基対反復配列 / ミオトニン・プロテインキナーゼ / 神経・筋培養 / ミオシン / アクチン |
Research Abstract |
Results from this reserch project are as follows : (1) We clarified that (CTG) n repeaat expands during somatic differentiation of human cultured fibroblasts from myotonic dystrophy (DM) patients, but not from controls and the amount of DM protein kinase (DMPK) decreases accompanying with the expansion of (CTG) n repeat. (2) We synthesized polyclonal antibody against DMPK,which recoginized the full-length of DMPK and we clarified that DMPK is localized not only in neuromuscular junction and muscle spindle, but also in type I muscle fibers. Immunohistochemically DMPK is localized between myosin bands and not colocalized with SERCA II ATPase. Ultrastructurally DMPK is cearly localized in the terminal cisternae of sarcoplasmic reticulum (SR). In human cardiac muscle, DMPK is localized in corbular and junctional SRs. (3) In DM skeletal muscle, the amount of DMPK dramatically decreases in comparison with controls. DMPK-positive muscle fibers show typical DM pathological changes such as type I atrophy, central nuclei, nuclear chains and sarcoplasmic masses. By immunoelectron microscopy, swollen DMPK-positive SRs are detected in the early stages of DM muscle degeneration. From this study we conclude that SR is the primary affected site of the degeneration of DM skeletal muscle and the decreased DMPK might cause the disregulation of intracellular calcium metabolism, followed by DM muscle degeneration. (4) We studied the developmental expression of DMPK in aneurally cultured human muscles and contracting cross-striated muscle innervated with fetal rat spinal cord. We conclude that the expression of DMPK during development is under neuronal influence.
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