| Project/Area Number |
16K15120
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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 |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
篠崎 昇平 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (40622626)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | GSNOR / NO / 炎症 / S-ニトロソ化タンパク質 / 心臓 / マクロファージ / Nitric Oxide / Cytokine / S-nitrosylation / Heart / Macrophage / Sepsis / 分子生物学 / iNOS |
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| Outline of Final Research Achievements |
In order to elucidate the role of S-nitrosoglutathione reductase (GSNOR), we comprehensively analyzed S-nitrosated protein in GSNOR KO mice using the heart of a sepsis model. As the results, we found numerous mitochondrial proteins and chaperone proteins which were markedly elevated in GSNOR KO mice, and among them mitochondrial localized chaperone protein X was actually S - nitrosated. In the analysis of macrophages in which GSNOR is highly expressed, the anti-inflammatory/anti-osteoclast differentiation effect was observed in GSNOR KO-derived macrophages, and the change in molecules such as NF-κB and c-Fos was important as a molecular mechanism. Our study identified two diametrically opposed function of GSNOR. GSNOR deficiency acts as anti-inflammatory properties on macrophage, while in heart GSNOR deficiency might be required for inflammation. Our results provide further insight into how a single protein can either function as inflammatory-promotor or inflammatory-suppressor.
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