Study on Cardiac Abnormality in hamster model of hereditary cardiomyopathy
| Project/Area Number |
05670645
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
SHIGEKAWA Munekazu National Cardiovascular Centar Research Institute, Dept.of Molecular Physiology, Head, 循環分子生理部, 部長 (00113738)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Toshitaro National Cardiovascular Center Research Institute Dept.of Molecular Physiology,, 循環分子生理部, レジデント
IWATA Yuko National Cardiovascular Center Research Institute Dept.of Molecular Physiology,, 循環分子生理部, 室員 (80171908)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Cardiomyopathy / Cardiomyopathic hamster / Dystrophin / Dystrophin-associated glycoprotein / Cytoskeleton / ハムスター / ジストロフィン結合蛋白質 |
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| Research Abstract |
1) In the ventricular muscle from 30-to 40-day-old Bio14.6 cardiomyopathic hamsters, the concentration of dystrophin was about 50% less than the normal controls. Despite its reduced content, extraction of dystrophin from the myopathic muscle into the microsomal fraction was threefold higher as compared to the control. These results suggest that abnormality exists in the association of dystrophin with sarcolemmal membranes in the myopathic muscle. No obvious difference, however, observed between normal and myopathic myocytes in their immunocytochemical staining patterns.
2) In ventricular muscle from 30-to 60-day-old cardiomyopathic hamsters, dystrophin-associated glycoproteins of 43,50 and 150 kDa are markedly reduced in abundance. In particular the 50 kDa glycoprotein is totally deficient in the sarcolemma of myopathic ventricular myocytes as revealed by immunofluorescence microscopy. The dystrophin-glycoprotein complex formation is defective in the cardiomyopathic hamster heart, becau
… More
se dystrophin and glycoprotein behave independently when digitonin-solubilized ventricular homogenates are fractionated on wheat germ agglutinin beads or antidystrophin immunoaffinity beads.
3) Dystrophin-dystrophin associated protein complex was isolated from digitonin-solubilized normal hamster cardiac muscle by a two-step method involving succinylated wheat germ agglutinin beads and anti-dystrophin antibody beads. While protein composition of the cardiac dystrophin associated protein complex was not differnt from that of the skeletal muscle counterpart, the protein yield of the cardiac complex was approximately 10 times as great. Unlike the skeletal complex, the cardiac complex could not be soulbilized from a microsomal fraction with 1% digitonin. These results indicates the difference in the property and content of cardiac versus skeltal dystrophin complex, suggesting a unique role for this protein complex in the cardiac muscle function.
4) We have investigated the distribution of the sarcolemmal Ca^<2+> transporters in hamster and dog ventricular myocytes by immunocytochemical and membrane fractionation techniques. The data suggest that the DHP receptor alpha1 subunit and the Na^+/Ca^<2+> exchanger are present in surface sarcolemma as well as T-tubule membranes located at the cardiac dyads. Compared with these Ca^<2+> transporters, the sarcolemmal Ca^<2+>-ATPase is much less abundant in the latter fraction. Thus the sarcolemmal Ca^<2+>-ATPase seems to be located predominantly in surface sarcolemma. Less
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Report
(3 results)
Research Products
(15 results)
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[Publications] Tawada-Iwata, Y., Imagawa, T., Yoshida, A., Takahashi, M., Nakamura, H., Shigekawa, M.: "Increased mechanical extraction of T-tubule/junctional SR from cardiomyopathic hamster heart." Am.J.Physiol.264. H-1447-H1453 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Iwata, Y., Nakamura, H., Mizuno, Y., Yoshida, M., Ozawa, E., Shigekawa, M.: "Defective association of dystrophin with sarcolemmal glycoproteins in the cardiomyopathic hamster heart." FEBS Lett.329. 227-231 (1993)
Description
「研究成果報告書概要(欧文)」より
Related Report
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