1997 Fiscal Year Final Research Report Summary
Pathophysiclogical mechanism of myotonic dystruphy
| Project/Area Number |
07670702
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KOBAYASHI Tadayoshi Tokyo Medical and Dental University, Department of Neurology, Assistant professor, 医学部, 講師 (70115343)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Myotonic dystrophy / myotonic dystrophy protein kinase / sarcoplasmic reticulum / trinucleatide repeat / skeletal muscle / cardiac muscle / immunohistochemistry / immunoelectron microscopy |
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| 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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[Publications] M. Shimokawa, S.Ishiura, N.Kameda, M.Yamamoto, N.Sasagawa, N.Saitoh, H.Sorimachi, H.Ueda, S.Ohno, K.Suzuki, T.Kobayashi: "Novel isoform of myotonior protein kinase:Gene product of myotonic dystrophy is localized in the sarcoplasmic reticulwne of skeletal muscle" Am,J.Pathol.150(4). 1285-1295 (1997)
Description
「研究成果報告書概要(和文)」より
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[Publications] Shimokawa M,Ishiura S,Kameda N,Yamamoto, M,Sasagawa N,Saitoh N,Sorimachi H,Ueda H,Ohno S,Suzuki K,Kobayashi T: "Novel isoform of myotonin protein kinase Gene product of myotonic dystrophy is localized in the sarcoplasmic reticulum of skeletal muscle." Am J Pathol. 150 (4). 1285-1295 (1997)
Description
「研究成果報告書概要(欧文)」より
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