| Project/Area Number |
12470185
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SUZUKI Norio Graduate School Of Medicine, The University of Tokyo, Professor, 大学院・医学系研究科, 教授 (10010050)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Kazuya School of Pharmacy, Tokyo university of Pharmacy and Life Science, Instructor, 薬学部, 講師 (80251221)
ENOMOTO Atsushi Graduate School Of Medicine, The University of Tokyo, Assistant, 大学院・医学系研究科, 助手 (20323602)
MATSUMOTO Yoshihisa TGraduate School Of Medicine, The University of Tokyo, Assistant, 大学院・医学系研究科, 助手 (20302672)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Ionizing radiation-induced apoptosis / SAPK / JNK / Ceramide / MOLT-4 / p41 specific antibody / MOLT-4細胞 / 放射線細胞死 / p53 / p41 |
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| Research Abstract |
The overall goal of the present project has been to analyze a mechanism of X-ray-induced apoptotic cell death in human T-cell leukemia cell line MOLT-4. Toward this goal, the purpose of the project were 1) to examine the involvement of p53 and/or SAPK/JNK, 2) to identify genes downstream of the p53 or SAPK/JNK, and to analyze the expressions of apoptosis-related genes by quantative RT-PCR methods, 3) to study a role of a new radiation-induced protein p41 in cell death.
1) To examine the involvement of ceramide-SAPK/JNK pathway, the effect of acid sphingomyelinase inhibitor (D609) on X-ray-induced apoptotic cell death was studied. D609 suppressed X-ray-induced apoptotic cell death as well as phosphorylation of JNK.
2) RT-PCR analysis of apoptosis-related genes revealed that the expression of c-myc gene was reduced following X-irradiation, but not in an X-ray-resistant variant cell line Rh-1a. The introduction of c-myc antisense oligonucleotides into MOLT-4 cells or the treatment of c-Myc inhibitor induced cell death.
3) Specific antibodies for p41 and p42 have been generated. Western blot analysis showed that the activation of caspase-9, caspase-7, and caspas-3 ran paralleled with the generation of p41. Especially, caspase-7 among those was considered important in p41 generation.
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