THE RELEVANCE OF THE SELECTIVE DAMAGE OF PURKINJE FIBER AND THE ABNORMAL ELECTROCARDIOGRAM IN CANINE X-LINKED MUSCLAR DYSTROPHY
| Project/Area Number |
16500283
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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 |
Laboratory animal science
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| Research Institution | NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY (NCNP) |
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Principal Investigator |
SHIMATSU Yoshiki NCNP, DEPARTMENT OF MOLECULAR THERAPY, SECTION CHIEF, 遺伝子疾患治療研究部, 室長 (90373406)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAHARA Masayoshi THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, ASSISTANT PROFESSOR, 大学院・農学生命科学研究科, 助教授 (30205273)
WAKAO Yoshito AZABU UNIVERSITY, SCHOOL OF VETERINARY MEDICINE, PROFESSOR, 獣医学部, 教授 (20063969)
TAKEDA Shin'ichi NCNP, DEPARTMENT OF MOLECULAR THERAPY, DIRECTOR, 遺伝子疾患治療研究部, 部長 (90171644)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | muscular dystrophy / canine X-linked muscular dystrophy / purkinje fiber / vacuolar degeneration / MuRF-1 / cardiac conduction / μ-calpain / ubiquitin / 空砲変性 / 心電図異常 |
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| Research Abstract |
In Duchenne muscle dystrophy (DMD), increase in the number of patients who die with the cardiac failure instead of the respiratory is recognized. There is a reason why the death rate of the respiratory decreases in the diffusion of respirators. A beagle based colony of canine X-linked muscular dystrophy (CXMD) dog in Japan designated CXMD_J shows skeletal muscle atrophy and weakness which is similar to DMD. Our main research subject has been to clear the mechanism of myocardial involvement in DMD using the CXMD_J dog. It doubted that the CXMD_J dog had the cardiac conduction abnormality since an abnormal Q wave of electrocardiogram and a sudden death due to the lethal arrhythmia were recognized. In the present study, the histopathological and immunohistochemical examination and the molecular determination after micro-dissection in the purkinje fiber were carried out. 1.The vacuolar degeneration of purkinje fiber was already observed before the working myocardium was involved. 2.The accumulation of calcium-dependent proteolysis, μ-calpain was observed in the purkinje fiber. 3.The cardiac Troponin I (cTnI) which was a substrate of μ-calpain was fragmented by μ-calpain and was isolated in the serum. 4.The cTnI which was a E3 ubiquitin ligase was fragmented by μ-calpain, and was ubiquitinated by the muscle-specific RING finger protein 1 (MuRF1) related to the skeletal muscle atrophy. The results of the present study suggest that the vacuolar degeneration of purkinje fiber in the CXMD_J dog was caused by the cTnI, and the cTnI was fragmented by the accumulation of μ-calpain and was broken down by the ubiquitin-proteasome pathway after the ubiquitination of MuRF1.
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Report
(3 results)
Research Products
(16 results)
