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Miura Yuri

    Proteome Research　Vice-director
Last Updated :2025/03/14

Researcher Information

J-Global ID

Research Areas

  • Life sciences / Biophysics
  • Life sciences / Functional biochemistry
  • Life sciences / Pharmaceuticals - health and biochemistry

Association Memberships

  • Japanese Proteomics Society   日本薬学会   日本基礎老化学会   SOCIETY FOR FREE RADICAL RESEARCH JAPAN   日本質量分析学会   日本電気泳動学会   

Published Papers

MISC

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2023/04 -2028/03 
    Author : 三浦 ゆり
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2026/03 
    Author : 梅澤 啓太郎; 三浦 ゆり
  • 糖鎖を基盤とした新たな認知症の健康管理システムの開発
    小柳財団：2023年度 研究助成
    Date (from‐to) : 2023/04 -2024/03 
    Author : 三浦ゆり
  • グライコミクス・グライコプロテオミクスによる健康長寿の機序の解明
    三井住友海上福祉財団：2022年度 研究助成
    Date (from‐to) : 2022/12 -2023/11 
    Author : 三浦ゆり
  • スプライシング調節によるエネルギー代謝の最適化を介した寿命制御
    日本学術振興会：科学研究費助成事業（基盤研究B）
    Date (from‐to) : 2020/04 -2023/03 
    Author : 樋上賀一
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2019/04 -2022/03 
    Author : Miura Yuri
     
    The purpose of this study was to clarify the biological significance of N-glycans associated with successful aging, and the mechanisms of healthy aging. We performed the observational study using a longitudinal cohort study for elderly people, and the validation study using genetically modified animals. In observational study, we examined the characteristic altered N-glycopeptides associated with diabetic cognitive impairment, and indicated that multi-branched and highly sialylated glycans, which were associated with successful aging, were decreased. In semi-super centenarians (SSCs) who are considered to accomplish successful aging, it was reported that diabetes was very rare and that age-related cognitive impairment was suppressed. Accordingly, these results might suggest that N-glycans associated with successful aging emerged in SSCs not as a result of extremely senescence, but as a factor of successful aging such as the suppression of age-related cognitive impairment.
  • 初期フレイルのバイオマーカー探索
    上原記念生命科学財団：研究助成
    Date (from‐to) : 2018/11 -2019/12 
    Author : 三浦ゆり
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/10 -2019/03 
    Author : OGAWA Yuko; YANOSHITA Ryohei; TSUJIMOTO Masafumi; GOTO Yoshikuni; IKEMOTO Mamoru; AKIMOTO Yoshihiro; MIURA Yuri; KUMEDA Nahoko
     
    Human whole saliva contains exosomes that have mucosal immunomodulatory potential. Immune-related proteins such as DPP IV and IgA, salivary proteins such as mucin 5B, and lipopolysaccharide (LPS) derived from oral bacteria were associated with surface of the exosomes. Mucin 5B was digested with gastrointestinal enzymes. Although IgA and LPS were dissociated by size-exclusion chromatography, a part of them was tightly associated with the exosomes. Salivary exosome without the surface molecules increased production of nitric oxide (NO) from murine macrophages. In addition, we found that DPP IV may contribute to the NO production by collaboration with LPS. Salivary exosome is presumed to suppress the excessive activation in oral cavity and cause the activation of mucosal immunity after exposure to the gastrointestinal condition.
  • 糖尿病合併症としての認知症に関する診断指標の開発と予防戦略への発展
    日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽）
    Date (from‐to) : 2018 -2019 
    Author : 岩本真知子、三浦ゆり、津元裕樹
  • 定量的O-GlcNAc修飾プロテオーム解析法を用いた糖尿病性腎症の病態解明と合併症予測マーカーの開発
    ノバルティスファーマ：2018年度ノバルティス研究助成
    Date (from‐to) : 2018 -2019 
    Author : 三浦ゆり
  • 健康長寿の指標となる糖鎖構造とその生物学的意義の解明
    日本学術振興会：科学研究費助成事業（基盤研究Ｃ）
    Date (from‐to) : 2016 -2019 
    Author : 三浦ゆり
  • 大規模長期縦断調査とプロテオミクス解析による初期フレイルのバイオマーカー探索
    三井住友海上福祉財団：研究助成金
    Date (from‐to) : 2016 -2017 
    Author : 三浦ゆり
  • 動脈老化と大動脈解離症におけるタンパク質発現・翻訳後修飾解析と病理組織学的解析
    日本学術振興会：科学研究費補助金（基盤研究Ｃ）
    Date (from‐to) : 2014 -2017 
    Author : 沢辺元司
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : Endo Tamao; Masami Miura; Miura Yuri; Keiko Manya
     
    α-Dystroglycanopathy is a type of congenital muscular dystrophies with neurological abnormality. Defect of O-mannosyl glycan on α-dystroglycan is a primary cause of α-dystroglycanopathy. In this study, we elucidated the precise structure of O-mannosyl glycan that contains ribitol 5-phosphate (Rbo5P); [GlcA-Xyl]n-Rbo5P-1Rbo5P-3GalNAcβ1-3GlcNAcβ1-4(phospho-6)Man. Rbo5P forms a tandem repeat and functions as a scaffold for the formation of the ligand-binding moiety. We also revealed that three α-dystroglycanopathy-causing proteins with unknown function, fukutin (Fukuyama Congenital Muscular Dystrophy), FKRP (Limb Girdle Muscular Dystrophy) and ISPD (Walker-Warburg syndrome), are involved in the synthesis of tandem Rbo5P. Fukutin and FKRP are Rbo5P transferases and ISPD synthesizes CDP-Rbo. We reported a novel O-mannosyl glycan structure and provided new insight into the molecular basis of its biosynthetic pathway and its role in nerve function in the brain.
  • シアル酸糖鎖のアンチエイジング効果の解析
    小柳財団：研究助成金
    Date (from‐to) : 2015 -2016 
    Author : 三浦ゆり
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013 -2014 
    Author : SAWABE Motoji; RHO Ayako; TODA Toshifusa; MIURA Yuri; TANAKA Hiroshi
     
    The aging-related arterial medial change (arterial aging) causes heart failure and chronic kidney disease in the elderly. Aortic dissection may arise from some unidentified anomaly of the aortic media. The purpose of this study is to analyze the changes of arterial medial constitutive proteins in arterial aging and aortic dissection using the comprehensive proteome analysis. In the cases of aortic dissection, there were increase and decrease of smooth muscle contraction proteins, increase of stress response proteins, and decrease of extracellular matrix proteins. Arterial aging was associated with decrease of smooth muscle actin, increase of stress response proteins, and increase of proteins of extracellular glycosaminoglycans. We successfully identified the specific changes of arterial medial constitutive proteins seen in arterial aging and aortic dissection.
  • プロテオミクス解析を用いた縦断調査による健康長寿マーカーの探索とその生物学的意義の解明
    三井住友海上福祉財団：研究助成金
    Date (from‐to) : 2013 -2014 
    Author : 三浦ゆり
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2008 -2011 
    Author : MIURA YURI
     
    In order to clarify the regulation mechanisms by O-GlcNAcylation in the signaling pathways caused by reactive oxygen species, the alteration of O-GlcNAcylated proteins due to oxidative stress and the effects of O-GlcNAcylation on the induction of stress responsive proteins were examined. The results suggest that O-GlcNAcylated proteins play a critical role of oxidative stress-responses, and that the induction of stress responsive protein is possible to be regulated by O-GlcNAcylation.
  • 機能プロテオミクスを用いた新規老化マーカーの開発と応用
    三井住友海上福祉財団：研究助成金
    Date (from‐to) : 2008 -2009 
    Author : 三浦ゆり
  • 放射線・紫外線適応応答マーカーを指標とした老化制御因子スクリーニング法の開発
    コスメトロジー研究振興財団：第19回研究助成
    Date (from‐to) : 2008 -2009 
    Author : 三浦ゆり
  • 神経細胞分化異常の改善を目指したレドックス応答制御因子としてのATMの分子機構解明
    持田記念医学薬学振興財団：第24回研究助成金
    Date (from‐to) : 2006 -2007 
    Author : 三浦ゆり
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2004 -2007 
    Author : MIURA Yuri
     
    We investigated low-dose irradiation-responsive proteins using proteomics on two-dimensional (2-D) PAGE, and the effects of aging on cell responses to radiation in variously aged rat astrocytes. After 5 Gy irradiation, the relative abundance of peroxiredoxin 2, an antioxidant enzyme, and latexin, an inhibitor of carboxypeptidase, increased. The induction of these proteins was suppressed by aging, suggesting that the response to high-dose radiation decreased with aging. The relative abundance of elongation factor 2 (EF-2) fragment increased 3 h and reduced 24 h after 0.1 Gy irradiation. Temporal enhancement of the EF-2 fragment due to low-dose irradiation was suppressed by aging. Since radiation adaptive response in cultured astrocytes was observed 3 h but not 24 h after 0.1 Gy-irradiation and suppressed by aging as previously reported, alteration of the EF-2 fragment corresponded to the radiation adaptive response. We also examined phospho-protein profiles, resulting in the relative abundance of phospho-EF-1β and phospho-β-actin being altered by 0.1 Gy-irradiation; however, aging did not affect the alteration of phospho-EF-141 and phospho-β-actin, unlike the EF-2 fragment. The results suggested that the EF-2 fragment was a possible candidate for the protein responsible for the radiation adaptive response in cultured astrocytes.
  • 放射線応答の先行指標となるタンパクの網羅的解析とその制御
    日本宇宙フォーラム：地上研究公募（宇宙利用先駆研究）
    Date (from‐to) : 2004 -2006 
    Author : 三浦ゆり
  • 日本学術振興会：科学研究費補助金（若手研究B）
    Date (from‐to) : 2001 -2003 
    Author : 三浦ゆり
     
    平成14年度は、低レベル酸化的ストレスによる細胞応答を分子レベルで明らかにするため、細胞内シグナル伝達経路の解明とプロテオーム解析の両面から解析した。 1.若齢ラットのグリア細胞で認められた適応応答は、ataxia-telansiectasia mutated(ATM)及びDNA-依存性プロテインキナーゼ(DNAPK)の欠損あるいは変異マウスの細胞では認められないことから、この適応応答にはATM及びDNAPKが関与していることが示唆された。そこで、これらの基質であり細胞周期の制御やアポトーシスシグナルの要であるp53に着目し、低レベル酸化ストレスによるp53のリン酸化とそれに及ぼす加齢の影響について検討した。月齢の異なるラットからグリア細胞を培養し、0.1Gyあるいは5GyのX線を照射した後、経時的にタンパクを抽出し、抗phospho-p53抗体を用いたウェスタンブロットにより解析した。その結果、5GyのX線照射により、若齢ラット及び老齢ラットのグリア細胞でp53は速やかにリン酸化され、このリン酸化には加齢の影響はほとんど認められなかった。また、0.1Gy照射によってもp53はリン酸化されることが明らかになった。 2.低レベル酸化ストレスによるタンパク発現の変化を調べるため、細胞から全タンパク質を抽出し二次元電気泳動によるプロテオーム解析を行った。一次元目は固定化pH勾配等電点電気泳動、二次元目はSDS-PAGEを行い、銀染色した後、画像解析ソフト(PDQuest)を用いてディファレンシャルディスプレーを行った。タンパクの同定は、CYPRO-Rubyにより蛍光染色した後、スポットカッターを用いてゲルを切り出し、トリプシン消化後MALDI-TOF質量分析装置を用いてペプチドマスフィンガープリンティングを行い、データベースと照合した。過酸化水素1μM処理により、若齢ラットの細胞で発現が変動するスポットを見いだした。このスポットの発現増加量及び時間経過は、老齢ラットの細胞では若齢ラットの細胞と異なっていた。
  • 日本学術振興会：科学研究費補助金（奨励研究A）
    Date (from‐to) : 1999 -2001 
    Author : 三浦ゆり
     
    本年度は、前年度報告した若齢ラットの培養グリア細胞における低線量放射線適応応答の分子機構を明らかにするため、種々の情報伝達因子を欠損した細胞を用いて検討を行った。まず、DNA依存性プロテインキナーゼ(DNA-PK)に変異を持つスキッドマウス(CB-17,scid/jcl)と正常なDNA-PK活性を持つCB-17マウスのグリア細胞を調べたところ、CB-17マウスの細胞では放射線適応応答が認められたが、スキッドマウスの細胞では認められなかった。また、Ataxia-Telangiectasia Mutated(ATM)をノックアウトしたマウスのグリア細胞とそのWild Typeのマウス(129sv)の細胞で同様の実験を行ったところ、wild typeのグリア細胞では認められる放射線適応応答が、ATMノックアウトマウスの細胞では認められなかった。以上の結果から、グリア細胞の細胞増殖における放射線適応応答には、DNA-PK及びATMタンパクが関与している可能性が示唆された。 また、放射線適応応答の機構を酵素レベルで解析するため、低線量放射線照射による抗酸化酵素の変動を調べた。その結果、MnSOD mRNAレベルは、若齢及び老齢ラットの細胞ともに低線量照射による有意な変動はなかった。また、その他の抗酸化酵素活性は、若齢ラットの細胞で、低線量照射により増加する傾向にあるものの有意な増加とは認められず、低線量放射線照射による抗酸化酵素の誘導がこの放射線適応応答の直接的な原因であるとは考えにくいことが明らかになった。 以上の結果から、本研究では培養グリア細胞で細胞増殖を指標とした放射線適応応答が認められること、またこの細胞応答は老化により影響を受けることを明らかにした。また、放射線適応応答の機構としてプロテインキナーゼC、DNA-PK及びATMタンパクが関与している可能性が示唆された。
  • 培養グリア細胞における低線量放射線の影響に関する研究
    日本宇宙フォーラム：地上研究公募（フェーズI B萌芽的研究）
    Date (from‐to) : 1999 -2000 
    Author : 三浦ゆり
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 1991 -1993 
    Author : UTSUMI Hideo; NAGAOKA Hiroaki; MIURA Yuri; TAKESHITA Keizo
     
    The several techniques for ESR imaging have been developed. The conventional methods for ESR-CT are based on the assumption that only one spectralcomponetn is existing in all space observed. No image can be constructed if more than two signal componets are coexisting in different part. In order to accomplish the image construction from plural signal components, we tried to connect spectral-spatial imaging technique with CT imaging. 1. We report the ESR-CT imaging by the phantom involving two radical species giving different signals. Spectral-spatial images obtained on four derections in X-Z plane. The spatial information was separated from the spectral-spatial images by each radical component. Two separation methods were compared. In one method, separation could not be complete. The border was broadened in other method. Two sets of CT images of two signal components were reconstructured. CT images have good agreement with arrangement of phantom. 2. The phantom involving liposomes which encapsulated nitroxide (150 mM) and free nitroxide (3.3mM) was made. We obtained the ESR-CT imaging by L-band ESR.CT images have good agreement with the distribution of loposomes and free nitroxide. These results demonstrate the possibility of ESR-CT for the sample including plural signal components.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 1990 -1992 
    Author : HAMADA Akira; MIURA Yuri; TAKESHITA Keizo; UTSUMI Hideo
     
    In order to utilize in vivo ESR-CT for studying drug-distribution and free radical reaction in biological system, we tried to measure ESR spectra of nitroxides administered into femoral muscle in mice, and obtained the following results. 1. Diffusion of spin-labeled compounds in muscle : Spin-labeled compound was injected into femoral muscle in mice.The resulting ESR spectrum seemed to be consisted of several components, which was due to different concentration of spin-labeled compound each other. Analysis of the spectrum with computer simulation indicated that the diffusion of nitroxide compounds in femoral muscle could be monitored with in vivo ESR. The signal of amino-TEMPO in femoral muscle of mice was decayed during occlusion, while that of Carbamoyl-PROXYL decreased only after reperfusion, suggesting that amino-TEMPO lose their paramagnetism in femoral muscle and Carbamoyl-PROXYL was transferred from muscle to blood. 2. ESR-CT system : One dimensional imaging of nitroxide administered into femoral muscle of mice was performed, suggesting that in vivo ESR-CT system may be applied to the study of drug-delivery-system. 3. Nitroxide reduction by ischemia-reperfusion injury : We prepared ischemia-reperfusion injury model by occlusion and reperfusion of the femoral thigh with a thread. The effects of ischemia-reperfusion on the reduction of nitroxides in femoral muscle were investigated by in vivo ESR, suggesting that nitroxides were reduced by active oxygen species produced by ischemia-reperfusion. 4. Improvement of ESR-CT system : To analyze the ESR spectrum containing several signals, spectral-special imaging system was developed.
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 1991 -1991 
    Author : 三浦 ゆり

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