| Project/Area Number |
09680618
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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 |
Functional biochemistry
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| Research Institution | Osaka University |
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Principal Investigator |
IKEUCHI Toshihiko Osaka University, Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (20093362)
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| Co-Investigator(Kenkyū-buntansha) |
HATANAKA Hiroshi Osaka University, Institute for Protein Research, Professor, たんぱく質研究所, 教授 (60208519)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Nerve Growth Factor / Brain-devived Neurotrophic Factor / Trk Receptor / Signal Transduction / Neuron / Neuronal Differentiation / Prevention of Apoptosis |
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| Research Abstract |
Cultured cerebellar granule neurons maintained in medium containing 26 mM potassium (high K^+ or HK^<>) undergo cell death when switched to medium with 5 mM potassium (low K^+ or LK^+).This low K^+-induced cell death has typical features of apoptosis has been investigated.Cerebellar granule neurons become committed to undergo apoptosis between 2 and 5 h after K^+ deprivation, judging from the inability of high K^+ to rescue them after this time.Although the levels of most mRNAs decrease markedly concomitant with commitment, expression of c-jun mRNA increases 2-3 h after K^+ deprivation.Among the family of caspases, a caspase-3-like protease is activated within 4 h of lowering the K^+ concentration.Inhibition of phosphatidylinositol 3-kinase (PI3-K) activity by LY294002 or wortmannin also induces apoptosis in cerebellar granule neurons.The intracellular signaling pathway of LY294002-induced apoptosis has been investigated.The activity of c-Jun N-terminal kinase (JNK) increases 8 h after addition of LY294002 to high K^+ medium of low K^+ medium containing BDNF.Expression of c-Jun protein also increases almost simultaneously.The low K^+-induced apoptosis of cerebellar granule neurons is prevented by high K^+ (membrane depolarization by high K^+), BDNF or cAMP.The intracellular signaling pathways by which these agents prevent low K^+-induced apoptosis have been investigated.High K^+ and BDNF prevent apoptosis through PI3-K and Ser/Thr kinase, Akt/PKB.The survival-promoting effect of cAMP does not on the PI3-K-Akt pathway.
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