| Project/Area Number |
08680857
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
SANO Mamoru Institute for Developmental Research, Department of Morphology, Section Chief, 形態学部, 室長 (60090429)
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| Co-Investigator(Kenkyū-buntansha) |
KITAJIMA Satoko Institute for Developmental Research, Department of Morphology, Research Assista, 形態学部, 研究助手
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | PC12D cells / neurite outgrowth / MAP kinase / trichostatin A / NGF / PC12D cells / 神経成長因子 / PC12D細胞 / MAPキナーゼ |
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| Research Abstract |
i.We have examined the local control by NGF of the outgrowth of neurites from PC12D cells. The observations suggest that the NGF-dependent maintenance or extension of neurites might be controlled within the neurites themselves and might not be require the direct involvement of the cell body (ref.no.2).
ii.Trichostatine A (TSA) at 100 nM selectively blocked the NGF- and b-FGF-induced outgrowth of neurites from PC12D cells, but not the outgrowth induced by abcAMP or staurosporine. This study also provides proof that NGF-induced elongation of neurites does not require protein synthesis de novo (ref.no.1).
iii.When PC12D cells were transfected with the dominant inhibitory Ha-ras Asn-17 gene, the induction of the mutant Ras led the suppression of the rapid outgrowth of neurites in response to NGF but not to abcAMP.The results implies a direct involvement of Ras protein in in the NGF-induced signal transduction that lead to the formation of neurites in PC12D cells (ref.no.3).
iv.We examined the effects of a specific inhibitor of the MAP kinase kinase (MEK) (PD98059) on the NGF-induced outgrowth of neurites in PC12D cells. The increase of MAP kinase activity in response to NGF was reduced by 80% upon treatment of PC12D cells with 50 muM PD98059, whereas the NGF-dependent formation of ruffles and the subsequent outgrowth of neurite were not blocked. The outgrowth of neurites from conventional PC12 cells by NGF was suppressed by the addition of 50 muM PD98059. In contrast, the rapid regeneration of neurites from PC12 cells primed with NGF,was not altered in the presence of the same dose of the inhibitor. It appeared that the activation of MAP kinase pathway was not necessarily required for the NGF-dependent extension of neurites (ref.no.3, ref no.4).
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