Project/Area Number |
63570376
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Neurology
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Research Institution | Institute for Developmental Research, Aichi Human Service Center |
Principal Investigator |
KATOH Ritsuko Chief Researcher Department of Perinatology, Institute for Developmental Research, Aichi Prefecture Colony, 主任研究員 (80100163)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUI Fumiko Research Assistant Department of Embryology, Institute for Developmental Researc, 研究助手
|
Project Period (FY) |
1988 – 1990
|
Project Status |
Completed (Fiscal Year 1990)
|
Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
|
Keywords | PC12 cells / Nerve growth factor / Neuritic growth / Proteoglycan / Extracellular matrix / Heparan sulfate / Chondroitin sulfate |
Research Abstract |
Biological functions of proteoglycans through the development of the nervous tissues were investigated from two points : 1) Changes in proteoglycans during the morphologic differentiation of neuronal cells and 2) effect of glia-derived proteoglycans on neuronal cell growth and differentiation. PC12 cells and brain chondroitin sulfate proteoglycans (CSPGs) were used for these purposes. The following was observed in PC12 cells : 1. PC12 cells synthesized two types of proteoglycans such as a heparan sulfate proteoglycan (HSPG) and a chondroitin sulfate proteoglycan (CSPG). 2. In PC12 cells differentiated nerve growth factor, cell-associated HSPG was larger in the amount per membrane than in the non-differentiated cells. The molecular size of HS was smaller and the concentration of N-sulfated residue of HS was higher than in the control cells. Furthermore,in the differentiated cells, a new type of HSPG with core protein of 51K in molecular size was synthesized in addition to that with 61K. A
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ll changes were observed preceding the elongation of neurites from PC12 cells. A flat-shaped variant of PC12 cells, PC12D cells synthesized cell-associated HSPG similar to that produced by differentiated PC12 cells. Therefore, these qualitative and quantitative changes of HSPG are considered to be related with cell adhesion. 3. Most proteoglycans released into the culture medium were CSPGs. CSPG with a core protein of 105 K and CSPG with a high content of sulfate residue were released into the medium from the differentiated PC12 cells, larger in the amount than those released into the control medium. The concentration of the latter CSPG increased during the neurite elongation. 4. Brain CSPGs, mostly derived from glial cells, inhibited the growth and neurite elongation of PC12D cells. The core proteins of CSPGs exerted these inhibitory effects. These results indicate that 1) qualitative and quantitative changes of PGs do occur during the neuritogenesis from PC12 cells induced by nerve growth factor and 2) glia-derived CSPGs has active biological effects on neuronal cells. Less
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