Functional analysis of low molecular weight stress protein in the central nerves
| Project/Area Number |
11672181
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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 |
Biological pharmacy
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| Research Institution | SHOWA UNIVERSITY |
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Principal Investigator |
NUMAZAWA Satoshi School of pharmaceutical Sciences, SHOWA UNIVERSITY Associate Professor, 薬学部, 助教授 (80180686)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Heme Oxygenase / HSP27 / Neural Cell Death / Oxidative Stress / PC12 / ストレス / 熱ショックタンパク質 / 中枢神経 / 4-ヒドロキシノネナール / プロティンキナーゼC |
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| Research Abstract |
The aim of this research was to clarify the function of the low molecular weight stress protein, such as heme oxygenase-1 (HO-1) and 27 kD heat shocking protein (HSP27), in the central nervous. The cell protection function of these low molecular weight stress proteins was investigated using rat pheochromocytoma PC12 cells, which conditionally express HO-1 and HSP27 in response to doxycycline. The apoptotic cell death induced by serum removal was suppressed by HSP27, whereas HO-1 showed no effect. Moreover, expression of these low molecular weight stress proteins showed no protective function in cells treated with compounds that induce oxidative stress and genotoxicity. Differentiated cells induced by nerve growth factor (NGF), on the other hand, showed increased susceptibility to hydrogen peroxide, most provably by reduced contents of cellular glutathione. Forced expression of HO-1 in these cells induced cell death, which was further increased by the low concentration of an HO-1 substrate hemin. This effect of hemin was canceled by deferoxamine, an iron-chelating agent. These results indicate that a molecular chaperon HSP27 counteracts apoptosis induced by growth factor starvation in PC12 cells. On the other hand, it is suggested that HO-1 induced by oxidative stress not only shows no a protection function in undifferentiated cells but also promotes cell death in differentiated cells through iron production by the enzyme reaction.
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Report
(2 results)
Research Products
(11 results)
