Regulation of redox signaling by reactive sulfur species in nervous system
Project/Area Number |
16H04674
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Osaka Prefecture University |
Principal Investigator |
Ihara Hideshi 大阪府立大学, 理学(系)研究科(研究院), 教授 (60254447)
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Co-Investigator(Kenkyū-buntansha) |
澤 智裕 熊本大学, 大学院生命科学研究部(医), 教授 (30284756)
中嶋 秀満 大阪府立大学, 生命環境科学研究科, 准教授 (30405360)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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Keywords | 活性イオウ分子 / レドックスシグナル / 神経変性 / 活性イオウ分子種 / 細胞内情報伝達 / レドックッスシグナル |
Outline of Final Research Achievements |
It had become obvious that ROS/redox signaling is pathophysiologically important in the nervus system. However, little was known about the role of reactive sulfur species, which is endogenous regulator of ROS/redox signaling. We used MeHg as an environmental electrophile and found that exposure of cells to the exogenous electrophile elevated intracellular concentrations of 8-nitro-cGMP, accompanied by depletion of reactive persulfide species and 8-SH-cGMP which is a metabolite of 8-nitro-cGMP. Exposure to MeHg also induced S-guanylation and activation of H-Ras followed by activation of MAPK and injury to cerebellar granule neurons. The electrophile-induced activation of redox signaling and the consequent cell damage were attenuated by pretreatment with a reactive persulfide species donor. Our results suggest that reactive persulfide species may be potential therapeutic targets for attenuating neurodegeneration.
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Academic Significance and Societal Importance of the Research Achievements |
メチル水銀を用いた酸化ストレスを介する神経変性疾患モデルで、神経毒性の発現にレドックスシグナルの亢進と細胞内の活性イオウ分子種の枯渇が一因であることを明らかにした。また、外因的活性イオウ分子ドナーによる細胞内活性イオウ分子の補充が、神経毒性を緩和することを明らかにしている。これらの結果は、活性イオウ分子が神経変性疾患の治療ターゲットになることを示唆している。また、新規の活性イオウ分子ドナーの開発、活性イオウ分子の生合成酵素の同定も行っているので、今後これらの知見をベースにした神経変性疾患に対する新たな治療戦略が展開されることが期待される。
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Polysulfide stabilization by tyrosine and hydroxyphenyl-containing derivatives that is important for a reactive sulfur metabolomics analysis.2019
Author(s)
Hamid HA, Tanaka A, Ida T, Nishimura A, Matsunaga T, Fujii S, Morita M, Sawa T, Fukuto JM, Nagy P, Tsutsumi R, Motohashi H, Ihara H, Akaike T.
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Journal Title
Redox Biol
Volume: 21
Pages: 101096-101096
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach2017
Author(s)
keda, M. Ishima, Y. Shibata, A. Chuang, V. T. G. Sawa, T. Ihara, H. Watanabe, H. Xian, M. Ouchi, Y. Shimizu, T. Ando, H. Ukawa, M. Ishida, T. Akaike, T. Otagiri, M. Maruyama, T.
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Journal Title
Analytica Chimica Acta
Volume: 969
Pages: 18-25
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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