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Development of preventive markers for cerebrovascular disease using novel oxidized modification products of proteins

Research Project

Project/Area Number 26350907
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionJuntendo University

Principal Investigator

Yamakura Fumiyuki  順天堂大学, 国際教養学部, 特任教授 (20053358)

Co-Investigator(Kenkyū-buntansha) 川崎 広明  順天堂大学, 医学(系)研究科(研究院), 特任研究員 (40531380)
飯泉 恭一  順天堂大学, スポーツ健康科学部, 助手 (30439351)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsニトロトリプトファン / 酸化傷害 / 脳卒中易発性高血圧発症ラット / アポリポプロテインE / arginosuccinate synthase / アポリポプロテインE / コレステロール / ニトロ化ストレス / 脳卒中易発性自然発症高血圧ラット / SHR-SP / 肝臓 / アポEタンパク質 / SHR
Outline of Final Research Achievements

Oxidative stress is known to participate for development of cardiovascular diseases. We have developed a new marker for oxidative stress, which is 6-nitrotryptophan (NO2Trp). We have applied this method for stroke-prone spontaneously hypertensive rat, SHRSP. We have found NO2Trp in apolipoprotein E (ApoE), in serum from SHRSP at 18 weeks of age, just before onset of the stroke. In order to clarify the relation between tissue injury and NO2Trp in ApoE, we have checked heart, brain, liver, and kidney of the SHRSP. However, we could not observed NO2Trp in ApoE in each of the tissues. Instead, we observed four other proteins in heart, 5 other proteins in brain, 10 other proteins in liver as NO2Trp containing proteins. Among them, arginosuccinate synthase in liver is important, because this enzyme is known to control formation of nitric oxide, an important regulator of hypertension. Therefore, nitration of this enzyme may participate formation of hypertension, at least partly, in SHRSP.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Int'l Joint Research] The Heart Research Institute, Sydney(オーストラリア)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Accumulation of immunoglobulin G against Dermatophagoides farinae tropomyosin in dorsal root ganglia of NC/Nga mice with atopic dermatitis-like symptoms.2017

    • Author(s)
      Otsu A, Kawasaki H, Tominaga M, Shigenaga A, Matsuda H, Takahashi N, Nakajima T, Naito H, Baba T, Ogawa H, Tomooka Y, Yamakura F, Takamori K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 485 Issue: 4 Pages: 707-712

    • DOI

      10.1016/j.bbrc.2017.02.109

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Peroxynitrite-mediated oxidation of plasma fibronectin2016

    • Author(s)
      Degendorfer G, Chuang CY, Kawasaki H, Hammer A, Malle E, Yamakura F, Davies MJ.
    • Journal Title

      Free Radic. Biol Med

      Volume: 97 Pages: 602-615

    • DOI

      10.1016/j.freeradbiomed.2016.06.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Electrophysiological properties of brain-natriuretic peptide- and gastrin-releasing peptide-responsive dorsal horn neurons in spinal itch transmission.2016

    • Author(s)
      Kusube F ,Tominaga M, Kawasaki H, Yamakura F, Naito H, Ogawa H, Tomooka Y, Takamori K,
    • Journal Title

      Neuroscience Letters

      Volume: 627 Pages: 51-60

    • DOI

      10.1016/j.neulet.2016.05.051

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Bioinformatic identification of cytochrome b5 homologues from the parasitic nematode Ascaris suum and the free-living nematode Caenorhabditis elegans highlights the crucial role of A. suum adult-specific secretory cytochrome b5 in parasitic adaptation.2015

    • Author(s)
      Takamiya S, Hashimoto M, Mita T, Yokota T, Nakajima Y, Yamakura F, Sugio S,
    • Journal Title

      Parasitol Int.

      Volume: 65 Issue: 2 Pages: 113-20

    • DOI

      10.1016/j.parint.2015.11.004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sumoylated α-skeletal muscle actin in the skeletal muscle of adult rats.2015

    • Author(s)
      Munehiro Uda、Hiroaki Kawasaki、Kyoichi Iizumi、Ayako Shigenaga、Takeshi Baba、Hisashi Naito、Toshitada Yoshioka 、Fumiyuki Yamakura
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 409 Issue: 1-2 Pages: 59-66

    • DOI

      10.1007/s11010-015-2512-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importance of the tryptophan nitration of carbonic anhydrase III for the morbidity of atopic dermatitis2014

    • Author(s)
      Hiroaki Kawasaki, Mitsutoshi Tominaga, Ayako Shigenaga, Atsuko Kamo, Yayoi Kamata, Kyoichi Iizumi, Utako Kimura, Hideoki Ogawa, Kenji Takamori, Fumiyuki Yamakura
    • Journal Title

      Free Radic Biol Med

      Volume: 73 Pages: 75-83

    • DOI

      10.1016/j.freeradbiomed.2014.04.034

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of substituting Trp for Leu t position 72 on the structure of Porphyromonas gingivalis superoxide dismutase2014

    • Author(s)
      Komachiya M, Mizoue S, Mihara M, Osawa M, Kikuchi Y, Uematsu S, HIrai K, Okubo Y, Kuroiwa A, Yamada K, Yamakura F, Hiraoka B Y
    • Journal Title

      Matsumoto Shigaku

      Volume: 40 Pages: 19-25

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Contribution of the amino acid resudues located near the active site metal to the metal-specific activity of Porphyromonas gingivalis SOD induced by a double mutation of Leu72Trp and Leu76Phe2014

    • Author(s)
      Mihara M, Komachiya M, Mizoue S, Osawa M, Uematsu S, Kikuchi Y, Okubo Y, Hirai K, Kuroiwa A, Yamada K, Yaakura F, Hiraoka BY,
    • Journal Title

      Matsumoto Shigaku

      Volume: 40 Pages: 26-34

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Localization of IgG against Dermatophagoides farina-tropomyosin in dorsal root ganglia of NC/Nga mice with atopic dermatitis-like symptoms2016

    • Author(s)
      Ayaka Otsu, Hiroaki Kawasaki, Mitsutoshi Tominaga, Ayako Shigenaga, Kyoichi Iizumi, Takeshi Baba, Hisashi Naito, Hideoki Ogawa, Tadaaki Nakajima, Yasuhiro Tomooka2 Fumiyuki Yamakura, Kenji Takamori
    • Organizer
      第41回日本研究皮膚科学会
    • Place of Presentation
      仙台
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 6-ニトロトリプトファン生成によCarbonic anhydrase IIIの機能傷害とアトピー性皮膚炎病態形成2016

    • Author(s)
      川崎広明、冨永光俊、松本綾子、飯泉恭一、馬場猛、大津彩夏、 楠部史也、池田啓一、髙森建二、山倉文
    • Organizer
      第37回日本トリプトファン研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 6-ニトロトリプトファンを指標としたアトピー性皮膚炎の早期検出2016

    • Author(s)
      飯泉恭一、川崎広明、冨永光俊、重永綾子、加茂敦子、鎌田弥生、髙森建二、山倉文幸
    • Organizer
      第37回日本トリプトファン研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] ペルオキシナイトライト修飾によるトリプシン及びキモトリプシンの酵素活性への影響,2016

    • Author(s)
      須藤絢音、池田啓一、重永綾子、川崎広明、興村桂子、小林淳、渡辺和人、酒口久尚、山倉文幸,
    • Organizer
      日本生化学会、第89回大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of 6-NO2Trp containing proteins in SHRSP-possible relation to hypertension2016

    • Author(s)
      Kawasaki H, Ikeda M, Sakai K, Matsumoto M, Iizumi K, Baba T, KTakamori K, Yamakura F
    • Organizer
      The16th International Union of Biochemistry and Molecular Biology Conference
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Studies on a novel biomarker for atopic dermatitis2016

    • Author(s)
      ) Iizumi K, Kawasaki H, Tominaga M, Shigenaga A, Kamo A, Kamata Y, Takamori K, Yamakura F
    • Organizer
      The16th International Union of Biochemistry and Molecular Biology Conference,
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ニトロ化ストレスとかゆみ〰アトピー性皮膚炎とニトロ化タンパク質2015

    • Author(s)
      川崎広明、山倉文幸
    • Organizer
      順天堂大学大学院医学研究科環境医学研究所 文部科学省平成25年度私立大学戦略的研究 基盤 形成支援事業 第2回公開シンポジュム
    • Place of Presentation
      本郷 東京
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 骨格筋で新たに見出された分子量の異なるa-アクチン の細胞内局在の検討2015

    • Author(s)
      宇田宗弘、川崎広明、飯泉恭一、重永綾子、馬場猛、内藤久士、 吉岡利忠、山倉文幸
    • Organizer
      第70回日本体力医学会
    • Place of Presentation
      和歌山県
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Nitration of tryptophan residues in proteins: Important roles in some diseases2015

    • Author(s)
      Yamakura F
    • Organizer
      International Society For Tryptophan Research Conference
    • Place of Presentation
      Grand Rapids, MI, USA
    • Year and Date
      2015-09-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 型糖尿病モデルマウスでのトリプトファンニトロ化による Glutathione s-transferaseの機能障害2015

    • Author(s)
      川崎広明、馬場猛、重永綾子、飯泉恭一、髙森建二、山倉文幸
    • Organizer
      第15回日本NO学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター、大阪
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 6-ニトロトリプトファン修飾免疫グロブリンはアトピー性 皮膚炎のマーカーになり得るか?2015

    • Author(s)
      飯泉恭一、冨永光俊、川崎広明、重永綾子、加茂敦子、鎌田弥生、 髙森建二、山倉文幸
    • Organizer
      第15回日本NO学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター、大阪
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 6-ニトロトリプトファンの血漿バイオマーカーとしての可能性-アトピー性皮膚炎2014

    • Author(s)
      飯泉恭一、冨永光俊、川崎広明、重永綾子、加茂敦子、鎌田弥生、髙森建二、山倉文幸
    • Organizer
      第36回日本トリプトファン研究会学術集会
    • Place of Presentation
      旭川医科大学
    • Year and Date
      2014-10-17 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 2型糖尿病モデルマウスにおける6-ニトロトリプトファンの生体内生成2014

    • Author(s)
      川崎広明、馬場猛、松本綾子、飯泉恭一、池田啓一、髙森建二、山倉文幸
    • Organizer
      第36回日本トリプトファン研究会学術集会
    • Place of Presentation
      旭川医科大学
    • Year and Date
      2014-10-17 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 骨格筋α-アクチンの新規翻訳後修飾2014

    • Author(s)
      田宗弘、川崎広明、飯泉恭一、重永綾子、馬場猛、内藤久士、山倉文幸
    • Organizer
      第69回日本体力医学会
    • Place of Presentation
      長崎大学文教キャンパス
    • Year and Date
      2014-09-19 – 2014-09-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳卒中易発性高血圧自然発症ラットSHR-SPでの6-ニトロトリプトファン生成 ~タンパク質機能傷害と病態形成の関連性の解明~2014

    • Author(s)
      川崎広明、池田雅彦、酒居一雄、重永綾子、飯泉恭一、宇田宗弘、馬場猛、髙森建二、山倉文幸
    • Organizer
      第14回日本NO学会学術集会
    • Place of Presentation
      ホテルニューオータニ佐賀
    • Year and Date
      2014-05-16 – 2014-05-17
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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