The role of S-nitrosylation for pathological mechanisms of metabolic syndrome.
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 |
Research Field |
Pathological medical chemistry
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Research Institution | Tokyo Medical and Dental University |
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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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Inflammatory stimuli induce inhibitory S-nitrosylation ofthe deacetylase SIRT1 to increase acetylation and activation of p53 and p65.2014
Author(s)
Shinozaki S, Chang K, Sakai M, Shimizu N, Yamada M, Tanaka T, Nakazawa H,Ichinose F, Yamada Y, Ishigami A, Ito H, Ouchi Y, Starr ME, Saito H, Shimokado K,Stamler JS, Kaneki M
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Journal Title
Sci Signal
Volume: 7
Issue: 351
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression.2013
Author(s)
Sips PY, Irie T, Zou L, Shinozaki S, Sakai M, Shimizu N, Nguyen R, Stamler JS, Chao W, Kaneki M, Ichinose F.
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Journal Title
Am J Physiol Heart Circ Physiol.
Volume: 304(8)
Related Report
Peer Reviewed
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