2013 Fiscal Year Final Research Report
Analysis of signaling pathway of novel lipid hydroperoxide dependent cell death
| Project/Area Number |
23590089
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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 |
Biological pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 細胞死 / 脂質酸化 / shRNAライブラリー / 化合物ライブラリー / GPx4 / 心不全 / ビタミンＥ |
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| Research Abstract |
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids From analysis of our tissue-specific PHGPx knockout mice, we clarified that depletion of PHGPx can induce novel cell death via generation of phospholipid hydroperoxide in several tissues. This novel lipid hydroperoxide dependent cell death can be completely suppressed by addition of vitamin E. To clarify the mechanism of novel cell death pathway, we screened chemical library and shRNA library using tamoxifen inducible PHGPx knockout MEF cells. We found six inhibitors and about 20 genes to suppress the novel lipid hydroperoxide dependent cell death.
Knockdown of target genes against inhibitors can be suppressed novel cell death. These identified genes were not different from that regulating apoptosis, necroptosis and autophagic cell death. These results means that lipid hydroperoxide dependent cell death is novel programmed cell death.
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Research Products
(24 results)
