1993 Fiscal Year Final Research Report Summary
Nerve Growth Factor-Induced Neurite Outgrowth and MAP Kinase
| Project/Area Number |
03670135
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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 |
General medical chemistry
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| Research Institution | Institute for Developmental Research, Aichi Colony |
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Principal Investigator |
SANO Mamoru Institute for Developmental Research, Department of Morphology, Section Chief, 究所, 室長 (60090429)
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| Co-Investigator(Kenkyū-buntansha) |
IWANAGA Misao Institute for Developmental Research, department of Morphology, Research Assista, 助手
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| Project Period (FY) |
1991 – 1993
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| Keywords | PC12D cells / neurites / MAP kinase / staurosporine |
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| Research Abstract |
i. When PC12D cells were cultured with NGF, outgrowth was neurites was promoted even when RNA synthesis was blocked. The outgrowth of neurites was also stimulated in response to fibroblast growth factor (FGF) and was slightly stimulated in response to epidermal growth factor (EGF). The close relationship between the activation of MAP kinase and outgrowth of neurites from PC12D cells in response to various agents suggests that activation of the kinase may play an important role in the outgrowth of neurites. Detailes were published in ref.no.1.
ii. When the supernatant fractions from extracts of control and NGF- or dbcAMP-treated PC12D cells were fractionated by DEAE-Sepharose column, enhancement of kinase activity in the 3rd peak that phosphorylate microtuble-associated proteins was noted in the case of the extracts from NGF-, FGF-, and of EGF-treated cells. The kinase activity in peak 1 was enhanced in the case of dbcAMP-treated cells. The observations strengthens the possibility of a c
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lose relationship between the outgrowth of neurites and and the activation of NGF-dependent MAP kinase. Detailes were published in ref. no.2.
iii. Rapid changes in morphology of PC12D cells in response to various agents were studied in relation to the subsequent outgrowth of neurites. Various neurite-promoting agents on PC12D cells caused ruffling around the periphery of cells and simultaneous relocalization of F-actin to the area of ruffles. The formation of ruffles might be one of the earliest steps of the neurite outgrowth and the morphological change might ge triggered by the activation of specific protein kinases. Detailers were published in ref.no.3.
iv. Staurosporine caused the rapid outgrowth of neurites from cultured dorsal root ganglia of chick embryos and from PC12D cells. the outgrowth of neurites were indistinguishable from those induced by NGF, as assessed by electron microscopy and and cytochemical staining of actin and tubulin. However, staurosporine never promoted survival of PC12D cells in serum-free conditions as that promoted by NGF.Detailes were published in ref.no.4. Less
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