| Project/Area Number |
14570605
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
IKEZOE Koji KYUSHU UNIVERSITY, Hospital, Research Associate, 大学病院, 助手 (80343317)
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| Co-Investigator(Kenkyū-buntansha) |
FURUYA Hirokazu KYUSHU UNIVERSITY, Graduated School of Medical Sciences, Associate Professor, 大学院・医学研究院, 助教授 (60253415)
TAKEDA Shinichi National Center of Neurology and Psychiatry, Institute of Neurosciencies, Head, 神経研究所, 部長(研究職) (90171644)
川尻 真和 九州大学, 医学部附属病院, 助手 (00335960)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | apoptosis / laminin-2 / merosin / anoikis / Bad / caspase-12 / ER stress / 小胞体ストレス性アポトーシス / 筋小胞体 / ジスフェルリン / 筋ジストロフィー |
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| Research Abstract |
Abortive regeneration process following massive necrosis in perinatal period causes dystrophic changes in laminin-2 deficient skeletal muscles. Although this apoptotic muscle fiber loss seems to be anchorage-dependent or anoikis, defective signaling pathways resulting in apoptosis have not been identified, yet.
In this study, we examined the signaling pathways disturbed in regenerating fibers of dy3K/dy3K, a null mutant mouse for laminin a2 chain. Regenerating fibers of dy3K/dy3K showed phosphorylation of Ser 112 and 135 of Bad, but of Ser 155. Ser 155 of Bad is phosphorylated via activation of PKA. Therefore, it is possible that the survival signaling pathway via PKA is disturbed in regenerating fibers of dy3K/dy3K.
In addition, we examined skeletal muscles in the pre-necrosis period of dy3K/dy3K. In dy3K/dy3K, massive necrosis occurs suddenly on postnatal day 10. We found the activation of caspase-12 on postnatal day 9. Accordingly, the endoplasmic reticulum (ER) stress-induced apoptosis seems to take place just before the necrosis of muscle fibers in dy3K/dy3K.
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