Regulation of bioenergy by NF-kB/IKKb signaling and oxidative stress-related diseases
| Project/Area Number |
16570121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | University of Hyogo |
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Principal Investigator |
KAMATA Hideaki University of Hyogo, Life Science, Assistant Professor, 大学院生命理学研究科, 助手 (10233925)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Hajime University of Hyogo, Life Science, Professor, 大学院生命理学研究科, 教授 (40049052)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Redox / Cancer / Inflammation / IKKb / Oxidative stress / NF-kB / Phosphatase / IKKBβ / NF-kB / MAPキナーゼホスファター / 活性酸素種 / 腫瘍壊死因子 / JNK / MKP / ネクローシス |
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| Research Abstract |
TNFα is a pleiotropic cytokine that can induce both cell proliferation and cell death. Inhibition of NF-κB activation increases susceptibility to TNFα-induced death. Exposure of NF-κB-deficient cells to TNFα, but not IL-1, also results in sustained JNK activation, an important contributor to the death response. The connection between NF-κB deficiency and sustained JNK activation was suggested to entail production of reactive oxygen species, such as H_2O_2. We now show that TNFα-induced H_2O_2 leads to oxidation and inhibition of JNK-inactivating phosphatases by converting their catalytic cysteine to sulfenic acid. This results in sustained JNK activation, which is required for cytochrome c release and caspase 3 activation. Treatment of cells or experimental animals with an antioxidant prevents H_2O_2 accumulation, JNK phosphatase oxidation, sustained JNK activity and caspase 3 activation. Antioxidant treatment also prevents TNFα-mediated fulminant liver failure without affecting liver regeneration.
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Report
(3 results)
Research Products
(32 results)
