| Project/Area Number |
25860231
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SHINOZAKI SHOHEI 東京医科歯科大学, 医歯(薬)学総合研究科, 寄附講座准教授 (40622626)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | S-ニトロソ化 / 慢性炎症 / 加齢関連疾患 / SIRT1 / メタボリックシンドローム / 一酸化窒素 / シグナル伝達 / インスリン抵抗性 |
|---|
| Outline of Final Research Achievements |
In aging-related diseases, chronic inflammation is associated with the increased production of nitric oxide. Nitric oxide causes a posttranslational modification of proteins known as S-nitrosylation. SIRT1 is a protein deacetylase that inhibits the transcription factors p53 and NF-κB, which are involved in mediating cell death by apoptosis and promoting inflammatory responses. S-nitrosylation inhibits SIRT1 activity. We found that in cultured mammalian cells, S-nitrosylation of SIRT1 prevented it from deacetylating and inhibiting p53 and NF-κB. In mouse models of systemic inflammation, neurodegeneration or muscle aging, S-nitrosylation of SIRT1 and the associated activation of p53 and NF-κB required the activity of nitric oxide synthases. Thus, S-nitrosylation of SIRT1 may be a critical factor in promoting apoptotic and inflammatory responses in aging-related diseases.
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