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Metabolism of ADMA, a novel risk factor of cardiovascular diseases and its pathophysiological role

Research Project

Project/Area Number 20590582
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionOkayama Prefectural University

Principal Investigator

KIMOTO Masumi  Okayama Prefectural University, 保健福祉学部, 教授 (40108866)

Co-Investigator(Kenkyū-buntansha) WAKINO Syu  慶應義塾大学, 医学部, 講師 (50265823)
YAMANISHI Rintaro  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (30253206)
Co-Investigator(Renkei-kenkyūsha) YAMASHITA Hiromi  岡山県立大学, 保健福祉学部, 教授 (70254563)
Research Collaborator YOKORO Miyuki  岡山県立大学, 大学院・保健福祉科学専攻, 博士後期課程2年
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords非対称性メチル化アルギニン / ADMA / DDAH / 一酸化窒素 / 内因性NOS阻害剤 / 動脈硬化症 / タンパク質アルギニンメチル化修飾 / 心血管疾患リスクファクター / 非対称ジチルアルギニン / 赤血球カタラーゼ / 動脈硬化 / PRMT1 / GARモチーフ / 翻訳後修飾 / 非対称ジメチルアルギニン / GAR モチーフ / 内因性NOS拮抗阻害剤 / N^6, N^6-dimethylarginine / 赤血球 / catalase
Research Abstract

We investigated the metabolic pathways of asymmetric dimethylarginine (ADMA) in blood cells to elucidate the regulatory mechanism of elevation of plasma ADMA, a novel risk factor of cardiovascular diseases. We found for the first time that ADMA was actively metabolized by PRMT1 and DDAH1 in erythrocytes and identified catalase that contains ADMA residue and interacts with PRMT1. These findings suggest that catalase is a potential target for methylation by PRMT1 in erythrocytes and may be a source of plasma ADMA.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (17 results)

All 2011 2010 2009 2008 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (11 results)

  • [Journal Article] Overexpression of dimethyl arginine dimethylaminohydrolase protects against cerebral vascular effects of hyperhomocysteinemia.2010

    • Author(s)
      Rodionov RN, Dayoub H, Lynch CM, Wilson KM, Stevens JW, Murry DJ, Kimoto M, Arning E, Bottiglieri T, Cooke JP, Baumbach GL, Faraci FM, Lentz SR.
    • Journal Title

      Circulation Res 106(3)

      Pages: 551-558

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of dimethylarginine dimethylaminohydrolase protects against cerebral vascular effects of hyperhomocysteinemia2010

    • Author(s)
      Rodionov, RN., et al.
    • Journal Title

      Circulation Res. 106

      Pages: 551-558

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial-specific dimethylarginine di methylaminohydrolase-1-deficient mice reveal that vascular endothelium plays an important role in removing asymmetric dimethylarginine.2009

    • Author(s)
      Hu X, Xu X, Zhu G, Atzler D, Kimoto M, Chen J, Schwedhelm E, Luneburg N, Boger RH, Zhang P, Chen Y.
    • Journal Title

      Circulation 120(22)

      Pages: 2222-2229

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial-specific dimethylarginine dimethylaminohydrol-ase-1-deficient mice reveal that vascular endothelium plays an important role in removing asymmetric dimethylarginine2009

    • Author(s)
      Hu X., et al.
    • Journal Title

      Circulation 120

      Pages: 2222-2229

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue-specific downregulation of dimethylarginine dimethylaminohydrol-ase in hyperhomocysteinemia.2008

    • Author(s)
      Dayal, s., et al.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol. 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of asymmetric dimethylarginine (ADMA)in tubulointestinal ischemia in early phase of diabetic nephropathy.

    • Author(s)
      Shibata, R., et al.
    • Journal Title

      Nephrol. Dial. Transplant. (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] タンパク質アルギニンメチル化転移酵素PRMT1 の高次構造と酵素機能の解析2011

    • Author(s)
      横路三有紀, 鈴木麻希子, 新垣友加里, 大塚智恵, 高橋吉孝, 山下広美, 辻英明, 木本眞順美
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] タンパク質アルギニンメチル化転移酵素PRMT1の高次構造と酵素機能の解析2011

    • Author(s)
      横路三有紀, 他7名
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都女子大学(京都府)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 赤血球カタラーゼはPRMT1 によるメチル化の主要な標的タンパク質である2010

    • Author(s)
      横路三有紀, 鈴木麻希子, 室田佳恵子, 大塚智恵, 高橋吉孝, 山下広美, 辻英明, 木本眞順美
    • Organizer
      第33回日本分子生物学会年会,第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] 赤血球における非対称性アルギニンメチル化タンパク質の産生と分解2010

    • Author(s)
      横路三有紀, 他6名
    • Organizer
      第64回日本栄養・食糧学会大会
    • Place of Presentation
      アスティとくしま(徳島県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Catalase is a major protein target of methylation with PRMT1 in erythrocytes2010

    • Author(s)
      Yokoro M., et al.
    • Organizer
      第33回日本分子生物学会年会 第83回日本生化学会大会合同大会:BMB2010
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 内因性NOS阻害剤ADMAの分解酵素, DDAHsの機能解析2009

    • Author(s)
      木本眞順美
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] ADMA, an endogeneous NOS inhibitor is metabolized activity in rat erythrocytes.2009

    • Author(s)
      横路三有紀, 鈴木麻希子, 高橋吉孝, 山下広美, 比江森美樹, 辻英明, 木本眞順美
    • Organizer
      10th International Symposium on Mechanism of Vasodilatation
    • Place of Presentation
      Miyagi, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] 内因性NOS 阻害剤ADMA の分解酵素,DDAHs の機能解析2009

    • Author(s)
      木本眞順美, 鈴木麻希子, 高橋吉孝, 横路三有紀, 山下広美, 比江森美樹, 辻英明
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report
  • [Presentation] ADMA, an endogenous NOS inhibitor is metabolized actively in rat erythrocytes2009

    • Author(s)
      Yokoro M., et al.
    • Organizer
      10^<th> International Symposium on Mechanism of Vasodilatation
    • Place of Presentation
      Matsushima, Miyagi Japan
    • Related Report
      2009 Annual Research Report
  • [Presentation] 内因性NOS阻害剤, ADMAの赤血球における代謝機構2008

    • Author(s)
      横路三有紀
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] ADMA代謝におけるDDAHsアイソフォームに特異的な触媒活性2008

    • Author(s)
      木本眞順美
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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