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Evaluation of the role of dihydrobiopterin in the regulation of endothelial function in the normal and pathological states

Research Project

Project/Area Number 24590324
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionUniversity of the Ryukyus

Principal Investigator

NOGUCHI Katsuhiko  琉球大学, 医学(系)研究科(研究院), 准教授 (70156181)

Co-Investigator(Kenkyū-buntansha) TSUTSUI Masato  琉球大学, 大学院医学研究科, 教授 (70309962)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords心血管 / 一酸化窒素 / 血管内皮細胞機能 / 酸化ストレス / 動脈硬化 / ジヒドロビオプテリン / テトラヒドロビオプテリン / dihydrofolate reductase / 血管内皮機能 / 一酸化窒素合成酵素
Outline of Final Research Achievements

An elevation of oxidized forms of tetrahydrobiopterin (BH4), especially dihydrobiopterin (BH2), has been reported in the setting of oxidative stress, such as atherosclerotic disorders, where endothelial nitric oxide synthase (eNOS) is dysfunctional, but the role of BH2 in the regulation of endothelial function in vivo remains to be clarified. This study was conducted to evaluate the effect of pharmacologically increased levels of BH2 on development of atherosclerotic lesion using a mouse arteriosclerotic model. Two-week treatment with sepiapterin and methotrexate increased aortic levels of BH2 doubly, but exacerbation of atherosclerotic lesion was not clearly found probably because of unspecific drug actions. Thus, to clarify the role of dihydrofolate reductase (DHFR), an enzyme catalyzing intracellular conversion of BH2 to BH4, in the regulation of endothelial function in vivo, we have been generating a novel mouse model with endothelial cell-specific deletion of DHFR gene.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Caffeine Contained in a Cup of Coffee Enhances Microvascular Endothelial Function in Healthy Subjects.2015

    • Author(s)
      Noguchi K, Matsuzaki T, Sakanashi M, Hamadate N, Uchida T, Kina-Tanada M, Kubota H, Nakasone J, Sakanashi M, Ueda S, Masuzaki H, Ishiuchi S, Ohya Y, Tsutsui M
    • Journal Title

      J Pharmacol Sci

      Volume: 127 Issue: 2 Pages: 217-222

    • DOI

      10.1016/j.jphs.2015.01.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse.2014

    • Author(s)
      Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Arakaki K, Kina-Tanada M, Kubota H, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Igarashi T, Ueno S, Matsushita M, Ishiuchi S, Masuzaki H, Ohya Y, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M.
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 77 Pages: 29-41

    • DOI

      10.1016/j.yjmcc.2014.09.021

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dihydrobiopterinによる内皮型一酸化窒素合成酵素機能障害2013

    • Author(s)
      野口 克彦、濱舘 直史、松﨑 俊博、坂梨 まゆ子、仲宗根 淳子、内田 太郎、新垣 久美子、久保田 陽秋、石内 勝吾、益崎 裕章、須加原 一博、大屋 祐輔、坂梨 又郎、筒井 正人
    • Journal Title

      琉球医学会誌

      Volume: 32 Pages: 7-12

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-Term Treatment With San’o-Shashin-To, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia-Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism2013

    • Author(s)
      Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Sakanashi M, Uchida T, Kina-Tanada M, Kubota H, Arakaki K, Tanimoto A, Yanagihara N, Sakanashi M, Ohya Y, Masuzaki H, Ishiuchi S, Sugahara K, Tsutsui M
    • Journal Title

      Circulation Journal

      Volume: 77 Issue: 7 Pages: 1827-1837

    • DOI

      10.1253/circj.CJ-12-1434

    • NAID

      10031173765

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ジヒドロビオプテリンのeNOS機能におよぼす影響2012

    • Author(s)
      野口克彦、松崎俊博、坂梨まゆ子、浜館直史、仲宗根淳子、坂梨又郎、筒井正人
    • Organizer
      第12回日本NO学会
    • Place of Presentation
      兵庫県、神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] ジヒドロビオプテリンによる生体位ラットのeNOS機能障害

    • Author(s)
      野口克彦、松崎俊博、坂梨まゆ子、浜館直史、仲宗根淳子、坂梨又郎、筒井正人
    • Organizer
      第13回日本NO学会
    • Place of Presentation
      那覇市
    • Related Report
      2013 Research-status Report
  • [Presentation] コーヒー1杯のカフェインのヒト微小血管内皮機能に対する急性効果

    • Author(s)
      野口克彦、松崎俊博、坂梨まゆ子、浜館直史、仲宗根淳子、坂梨又郎、筒井正人
    • Organizer
      第13回日本NO学会
    • Place of Presentation
      那覇市
    • Related Report
      2013 Research-status Report
  • [Presentation] 内皮型一酸化窒素合成酵素(eNOS)の新しい活性調節機構の解明:DihydrobiopterinによるeNOS機能不全

    • Author(s)
      野口克彦、松﨑俊博、坂梨まゆ子、仲宗根淳子、内田太郎、新垣久美子、久保田陽明、石内勝吾、益崎裕章、須加原一博、大屋祐輔、坂梨又郎、筒井正人
    • Organizer
      第157回琉球医学会例会
    • Place of Presentation
      沖縄県、西原
    • Related Report
      2012 Research-status Report
  • [Remarks] 琉球大学 大学院 医学研究科 薬理学

    • URL

      http://w3.u-ryukyu.ac.jp/pharmaco/Pharmacology/youkoso_yao_lihe.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 琉球大学大学院医学研究科薬理学

    • URL

      http://w3.u-ryukyu.ac.jp/pharmaco/Pharmacology/youkoso_yao_lihe.html

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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