Radiosensitization of radioresistant cancer stem cells by inhibition of ATM
| Project/Area Number |
23659588
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Tohoku University (2012-2013)
Hiroshima University (2011) |
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Principal Investigator |
HOSOI Yoshio 東北大学, 医学(系)研究科(研究院), 教授 (50238747)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 放射線 / 放射線感受性 / 活性酸素 / ATM |
|---|
| Research Abstract |
We report herein that ATM can be activated when exposed to hydrogen peroxide without inducing nuclear DDR in Hep G2 cells, and the oxidized cells could be subjected to subcellular fractionation. The first detergent-based fractionation experiment revealed that active, phosphorylated ATM was located in the second fraction, which also contained both mitochondria and peroxisomes. An alternative fractionation method involving homogenization and differential centrifugation, which permits the light membrane fraction containing peroxisomes to be produced, but not mitochondria, revealed that the light membrane fraction contained only traces of ATM. In contrast, the heavy membrane fraction, which mainly contained mitochondrial components, was enriched in ATM and active ATM, suggesting that the oxidative activation of ATM occurs in mitochondria and not in peroxisomes. In Rho 0-Hep G2 cells, which lack mitochondrial DNA and functional mitochondria, ATM failed to respond to hydrogen peroxide.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Evaluation of Zinc (II) chelators for inhibiting p53-mediated apoptosis2013
Author(s)
Morita A, Ariyasu S, Ohya S, Takahashi I, Wang B, Tanaka K, Uchida T, Okazaki H, Hanaya K, Enomoto A, Nenoi M, Ikekita M, Aoki S, Hosoi Y
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Journal Title
Oncotarget
Volume: 4
Pages: 2439-2450
URL
Related Report
Peer Reviewed
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[Journal Article] Evaluation of Zinc (II) chelators for inhibiting p53-mediated apoptosis.2013
Author(s)
Morita A, Ariyasu S, Ohya S, Takahashi I, Wang B, Tanaka K, Uchida T, Okazaki H, Hanaya K, Enomoto A, Nenoi M, Ikekita M, Aoki S, Hosoi Y
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Journal Title
Oncotaget
Volume: 4
Pages: 2439-2450
Related Report
Peer Reviewed
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