2002 Fiscal Year Final Research Report Summary
Analysis of MAP kinase cascades in inclusion body myositis
| Project/Area Number |
13670676
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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 | Kansai Medical University |
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Principal Investigator |
NAKANO Satoshi Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30333206)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Hidefumi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20250061)
KUSAKA Hirofumi Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (70250066)
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| Project Period (FY) |
2001 – 2002
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| Keywords | inclusion body myositis / MAP kinase / ERK / MAP kinase phosphatase / MAP kinase Kinase / phosphorylation |
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| Research Abstract |
Inclusion body myositis(IBM) is suggested to be the most common muscle disease among the elderly and refractory to various therapies including corticosteroids and immuno-suppressants. In some muscle fibers in biopsied muscles in IBM, there are inclusions that are abnormally phosphorylated. Based on this observation, we started to investigate the abnormality of phosporylation and dephosphorylation in IBM.
n this project, we have demonstrated perinuclear accumulation of extracellular signal-regulated protein kinase(ERK) that belongs to the MAP kinase family and its nuclear substrate, Elk-1 in abnormal fibers in IBM. We then tested activators and inactivators of MAP kinases in IBM. MAP kinase kinases that activate MAP kinases were not up-regulated in IBM. Among MAP kinase phosphatases that inactivate MAP kinase, MAP kinase phosphatase-1 was induced in abnormal fibers. The up-regulation of this phosphatase may probably be to down-regulate ERK.
These results suggest that perinuclear accumulation of ERK protein is due to impairment of nuclear translocation of ERK that is activated in physiological levels. We are currently investigating nuclear transport factors in IBM.
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[Publications] Nakamoto, M., Nakano, S., Kawashima, S., Ihara, M., Nishimura, Y., Shinde, A., Kakizuka, A.: "Unequal crossing-over in unique PABP2 mutations in Japanese patients-a possible cause of oculopharyngeal muscular dystrophy."Arch.Neurol.. 59. 474-477 (2002)
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[Publications] Wanschitz, J., Nakano, S..Goudeau, B., Strobel, T., Rinner, W., Wimmer, G., Resch, H., Jaksch, M., Akiguchi, I., Vicart,, Budka, H.: "Myofibrillar(desmin-related) myopathy : clinico-pathological spectrum in 3 cases and review of the literature."Clin.Neuropathol.. 21. 220-231 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakano, S., Shinde, A., Kawashima, S., Nakamura, S., Akiguchi, I., Kimura, J.: "Inclusion body myositis : expression of extracellular signal-regulated kinase and its substrate."Neurology. 56. 87-93 (2001)
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[Publications] Nakamura, S., Kawamoto, Y., Kitajima, K., Honjo, Y., Matsuo, A., Nakano, S., Akiguchi, I.: "Immunphistochemical localization of phosphoinositide 3-kinase in brains with multiple system atrophy."Clin.Neuropathol.. 20. 243-247 (2001)
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