Research about proteasome inhibitors-induced apoptosis in human glioma cells
| Project/Area Number |
10671333
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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 |
Cerebral neurosurgery
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
NAKANO Atsuhisa Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 助手 (70258151)
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| Co-Investigator(Kenkyū-buntansha) |
中野 敦久 兵庫医科大学, 医学部, 助手 (70258151)
KITAGAWA Hiroyuki
池本 秀康 兵庫医科大学, 医学部, 助手 (30278824)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Proteasome / Apoptosis / Glioma / ミトコンドリア / プロテアソーム阻害剤 / ヒト・グリオーマ / カスペースファミリー / Bcl-2ファミリー |
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| Research Abstract |
Proteasome inhibitors lactacystin and AcLLNal induced p53-independent apoptosis in two human glioma cell lines, and the apoptosis was accompanied by up-regulation of immunoreactive wild-type p53, p21ィイD1Waf1ィエD1, Mdm2, and p27ィイD1Kip1ィエD1. The pretreatment with cycloheximide decreased the induction of cell death independently of p53 protein status, suggesting that the up-regulation of short-lived proteins is associated with proteasome inhibitor-induced apoptosis. Caspase-3-like proteases were activated in the proteasome inhibitor-mediated apoptosis, and the induction of cell death was inhibited more effectively in the presence of z-VAD.fmk than in the presence of Ac-DEVD.fmk, suggesting that caspases other than caspase-3 are involved. Nonetheless, there was no significant alterations in levels of immunoreactive Bcl-2, Bcl-xィイD2LィエD2, Bax, Bad, and Bak, as well as no evidence of cyt c release into cytosol and dissipation of ΔψィイD2mィエD2. Thus, the proteasome inhibitor-induced apoptosis is mediated by mitochondria-independent mechanism, and the once activated caspase-3 does not cause the cyt c release and the ΔψィイD2mィエD2 disruption.
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Report
(3 results)
Research Products
(4 results)
