To clarify of the mechanism of thermotolerance
Project/Area Number |
18390335
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Radiation science
|
Research Institution | Nara Medical University |
Principal Investigator |
TAKAHASHI Akihisa Nara Medical University, Department of Biology, Shool of Medicine, Assistant Professor (60275336)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥8,020,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2007: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
|
Keywords | Radiation Oncology / Hyperthermia / Thermotolerance / DNA Double Strand Break |
Research Abstract |
Although heat shock proteins (HSPs) are well known to contribute to thermotolerance, they only play a supporting role in the phenomenon. Recently, it has been reported that heat sensitivity depends on heat-induced DNA double-strand breaks (DSBs), and thermotolerance also depends on the suppression of DSB formation. However the critical elements involved in thermotolerance have not yet been fully identified. Heat produces DSBs and leads to cell death through denaturation and dysfunction of heat-labile repair proteins such as DNA polymerase β (Polβ). Here we show that thermotolerance was partially suppressed in Polβ-/- mouse embryonic fibroblasts (MEFs) when compared to the wild type MEFs, and was also suppressed in the presence of the HSP inhibitor, KNK437, in both cell lines. Moreover, we found that heat-induced γH2AX was suppressed in the thermotolerant cells. These results suggest that Polβ at least contributes to thermotolerance through its reactivation and stimulation by Hsp27 and Hsp70. In addition, it appears possible that fewer DSBs were formed after a challenging heat exposure because pre-heat-induced Hsp27 and Hsp70 can rescue or restore other, as yet unidentified, heat-labile proteins besides Polβ. Our novel findings provide strong evidence that Polβ functions as a critical element involved in thermotolerance and exerts an important role in heat-induced DSBs.
|
Report
(3 results)
Research Products
(188 results)
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[Journal Article] γH2AX2008
Author(s)
Ohnishi T, et. al.
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Journal Title
Encyclopedia of Cancer. Springer (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] 温熱による分子損傷2008
Author(s)
Takahashi, A
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Journal Title
ハイパニサーミア-がん温熱療法ガイドブック-.毎日健康サロン出版 (in press)
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 温熱によるDNA二重鎖切断生成2007
Author(s)
高橋 昭久, et. al.
Organizer
第50回日本放射線影響学会
Place of Presentation
幕張メッセ,千葉
Year and Date
2007-11-17
Description
「研究成果報告書概要(和文)」より
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[Presentation] 染色体異常を指標とした放射線適応応答2007
Author(s)
高橋 昭久, et. al.
Organizer
第21回日本宇宙生物科学会
Place of Presentation
お茶の水女子大学,東京
Year and Date
2007-09-28
Description
「研究成果報告書概要(和文)」より
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[Presentation] 染色体異常を指標とした放射線適応応答2007
Author(s)
Takahashi A, et. al.
Organizer
21th Annual Meeting of the Japanes Society for Biological Sciences in Space
Place of Presentation
Ochanomizu University, Japan
Year and Date
2007-09-28
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] サカサナマズではlGでもμGでも背光反射は見られない2007
Author(s)
Ohnishi K, et. al.
Organizer
21th Annual Meeting of the Japanes Society for Biological Sciences in Space
Place of Presentation
Ochanomizu University, Japan
Year and Date
2007-09-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 各種細胞における温熱によるγH2AX誘導2007
Author(s)
高橋 昭久, et. al.
Organizer
第46回日本医学放射線学会生物部会学術大会
Place of Presentation
つくば国際会議場,筑波
Year and Date
2007-07-21
Description
「研究成果報告書概要(和文)」より
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[Presentation] 高LET放射線によるDNA損傷の傷跡2006
Author(s)
Takahashi A, et. al.
Organizer
20th Annual Meeting of the Japanes Society for Biological. Sciences in Space
Place of Presentation
Osaka City University, Janan
Year and Date
2006-09-29
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 温熱耐性とDNA二本鎖切断との関連2006
Author(s)
高橋 昭久, et. al.
Organizer
第12回癌治療増感研究会
Place of Presentation
富山国際会議場,富山
Year and Date
2006-05-19
Description
「研究成果報告書概要(和文)」より
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