| Project/Area Number |
24591835
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | University of Toyama |
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Principal Investigator |
ZHAO Qing-Li 富山大学, 大学院医学薬学研究部(医学), 助教 (90313593)
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| Research Collaborator |
FUJIWARA Yoshisada 富山大学, 大学院医学薬学研究部(医), 協力研究員(神戸大学名誉教授)
KONDO Takashi 富山大学, 大学院医学薬学研究部(医), 教授
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 細胞死 / 温熱 / 放射線 / 放射線治療生物学 |
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| Outline of Final Research Achievements |
In this study, we identified that Tempo combine treatment with hyperthermia rapidly induced autophagic cell death in U937 and HeLa cells. This co-treatment inhibited the processing of heat-activated procaspase-3 into active small subunits, leading to the inhibition of caspase-dependent apoptosis, and instead caused the induction of autophagy. The inactivation of caspases, a key event, could result from oxidation of active-site-CysSH of all caspases by a prooxidant oxo-ammonium cation, an intermediate derived Tempo during dismutation of hyperthermia-induced superoxide anion. In addition, the co-treatment caused mitochondrial dysfunction, and liberation of Beclin 1 from the Bcl-2/Beclin 1 complex, all of which contributed to induction of autophagy. These autophagic cells are leading to the complete proliferative inhibition. Thus, Tempo is a unique thermosensitizer to synergistically induce apoptosis and autophagic cell death.
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