| Project/Area Number |
03833026
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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 |
分子細胞生物学
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| Research Institution | SAGA MEDICAL SCHOOL |
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Principal Investigator |
KOEKI Tatsuro SAGA MED SCH, NATURAL SCI, PROFESSOR, 医学部, 教授 (80128131)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Shuuitsu SAGA MED, SCH, RESEARCH ASSOCIATE, 医学部, 教務員 (90202431)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Death / Degeneration / Nerve growth factor / Depolarization / cascade / 小脳 / 交感神経節 / 神経成長因子 / 分子生物学 / プロトオンコジン / PC12 / シクロヘキシミド |
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| Research Abstract |
PC12 cells undergo degeneration after nerve growth factor (NGF) withdrawal only when they have been treated with NGF Actinomycin D or cordycepin blocked the release of lactate dehyrogenase (LDH) activity up to 85-90%; the residual release was due to neurite degeneration. Thus, NGF deprivation-induced cell death of PC12 cells occurs in a transcription-dependent manner, while serum deprivation-induced PC12 cell death has been reported to be a transcription-independent process. The cell death was completely prevented by chronic depolarization with high potassium (>35mM), CPT-cAMP(>0.1mM), acidic and basic FGF(10ng/ml). Upon NGF deprivation, rapid dephosphorylation of major tyrosine-phosphorylated proteins, p120, p80, p70 as well as p140 trk occurred followed by gradual down-regulation of kinase activities (Ser/Thr) which appears to require RNA and protein synthesis. These results suggest that a dephosphorylation cascade initiated by trophic factor deprivation is highly reulated, and may constitute a part of programmed neuronal death cascade(s).
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