• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of DDAH, a metabolizing enzyme for endogenous NO inhibitor ADMA,in diabetic nephropathy : its therapeutic application

Research Project

Project/Area Number 19590938
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

TOJO Akihiro  The University of Tokyo, 医学部・附属病院, 講師 (50292917)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords糖尿病性腎症 / ADMA / DDAH / nitric oxide / eNOS / 酸化ストレス / angiotensin receptor blocker
Research Abstract

DDAHにはDDAH I とDDAH II の2つのisoformsが存在するが,血管内皮および平滑筋にはDDAH II が発現し, DDAH II のsiRNAにより血管拡張反応が抑制された。一方、DDAH I はほとんど発現がみられず, DDAH I siRNAの血管反応に及ばす効果はみられなかった。腎皮質ではDDAH I がDDAH II より発現が多く、DDAH I siRNAにより血中ADMA濃度が増加したが, DDAH II siRNAは血中ADMAには影響しなかった。腎臓ではDDAH I は近位尿細管に,DDAH II はmacula densa,遠位尿細管,血管平滑筋, 内皮に存在した。糖尿病性腎症ではDDAH I が減少し, 血中ADMAが増加した。Angiotensin receptor blocker(ARB) はDDAH I を増加し, ADMAを抑制し, Nobioavailabilityを改善した。ARBなどによるDDAH発現調節はADMA濃度を減少し, 腎血流量が増加し, 糖尿病性腎症の治療戦略となる。またARBはADMA産生に関与するPRMTを抑制した。研究の過程でアルブミンがendocytosisにより細胞内に取り込まれ, eNOS, DDAHなどの内皮機能やpodocyte障害に関与することが分かり, アルブミンendocytosisへ研究が派生した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (34 results)

All 2008 2007

All Journal Article (25 results) (of which Peer Reviewed: 23 results) Presentation (9 results)

  • [Journal Article] Expression of DDAH andPRMT isoforms in the diabetic rat kidney ; effects of angiotensin II receptor blocker2008

    • Author(s)
      Onozato ML, Tojo A, Leiper J, Fujita T,Palm F, Wilcox CS.
    • Journal Title

      Diabetes 57

      Pages: 172-180

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glomerular albumin filtration throughpodocyte cell body in puromycinaminonucleoside nephritic rat2008

    • Author(s)
      Tojo A, Onozato ML, Kitiyakara C, Kinugasa S, Fukuda S, Sakai T, Fujita T.
    • Journal Title

      Medical Molecular Morphology 41(2)

      Pages: 92-98

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Erythrophagocytosis by renal tubular cells2008

    • Author(s)
      Mimura I, Tojo A, Uozaki H, Fujita T.
    • Journal Title

      Kidney Int 74

      Pages: 398-398

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of dietary potassiumagainst vascular injury insalt-sensitive hypertension2008

    • Author(s)
      Kido M, Ando K, Onozato ML, Tojo A, Yoshikawa M, Ogita T, Fujita T.
    • Journal Title

      Hypertension 51(2)

      Pages: 225-31

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional and ImmunochemicalCharacterization of a Novel OrganicAnion Transporter Oat8 (Slc22a9) in RatRenal Collecting Duct2008

    • Author(s)
      Yokoyama H, Anzai N, Ljubojevic M,Ohtsu N, Sakata T, Miyazaki H, NonoguchiH, Islam R, Onozato M, Tojo A, Tomita K, Kanai Y, Igarashi T, Sabolic I, Endou H.
    • Journal Title

      Cell Physiol Biochem 21(4)

      Pages: 269-278

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] NoncrescenticANCA-associated renal crisis in systemic sclerosis2008

    • Author(s)
      Mimura I, Hori Y, Matsukawa H, UozakiH, Tojo A, Fujita T.
    • Journal Title

      Clin Nephrol 70

      Pages: 183-185

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] How tooptimize the treatment of a hypertensivepatient with multiple cardiovascularrisk factors2008

    • Author(s)
      Tojo A, Maristela L, Onozato, KensukeAsaba, and Toshiro Fujita
    • Journal Title

      Renin Angiotensin Systemin Cardiovascular Medicine 4(2)

      Pages: 16-18

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 腎疾患における内皮機能障害. DDAH-ADMA-NOS 系の役割2008

    • Author(s)
      宮崎博喜、藤乗嗣泰
    • Journal Title

      Nephrology Frontier 7

      Pages: 363-368

    • Related Report
      2008 Final Research Report
  • [Journal Article] Expression of DDAH and PRMT isoforms in the diabetic ratkidney; effects of angiotensin II receptor blocker.2008

    • Author(s)
      Onozato ML, Tojo A, Leiper J, Fujita T, Palm F, Wilcox CS
    • Journal Title

      Diabetes 57

      Pages: 172-180

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glomerular albumin filtration through podocyte cell body in puromycin aminonucleoside nephritic rat.2008

    • Author(s)
      Tojo A, Onozato ML, Kitiyakara C, Kinugasa S, Fukuda S, Sakai T, Fujita T.
    • Journal Title

      Medical Molecular Morphology 41

      Pages: 92-98

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Erythrophagocytosis by renal tubular cells.2008

    • Author(s)
      Mimura I, Tojo A, Uozaki H, Fujita T.
    • Journal Title

      Kidney Int 74

      Pages: 398-398

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of dietary potassium against vascular ijury in salt-sensitive hypertension.2008

    • Author(s)
      Kido M, Ando K, Onozato ML, Tojo A, Yoshikawa M, Ogita T, Fujita T.
    • Journal Title

      Hypertension. 51

      Pages: 225-231

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] How to optimize the treatment of a hypertensive patient with multiple cardiovascular risk factors.2008

    • Author(s)
      Akihiro Tojo, Maristela L. Onozato, Kensuke Asaba, Toshiro Fujita.
    • Journal Title

      Renin Angiotensin System in Cardiovascular Medicine. 4

      Pages: 16-18

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腎疾患における内皮機能障害.DDAH-ADMA-NOS系の役割.2008

    • Author(s)
      宮崎博喜、藤乗嗣泰
    • Journal Title

      Nephrology Frontier 7

      Pages: 363-368

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Expression of DDAH and PRMT isoforms in the diabetic ratkidney; effects of angiotensin II receptor blocker.2008

    • Author(s)
      Onozato ML, Tojo A, Leiper J, Fujita T, Palm F, Wilcox CS
    • Journal Title

      Diabetes

      Pages: 172-180

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-Specific Regulation byNG-NG-DimethylarginineDimethylaminohydrolase of Rat SerumAsymmetric Dimethylarginine andVascular Endothelium-Derived RelaxingFactor/NO2007

    • Author(s)
      Wang D, Gill PS, Chabrashvili T, OnozatoML, Raggio J, Mendonca M, Dennehy K, LiM, Modlinger P, Leiper J, Vallance P,Adler O, Leone A, Tojo A, Welch WJ, Wilcox CS.
    • Journal Title

      Circ Res 101(6)

      Pages: 627-635

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Double-edged action of SODmimetic in diabetic nephropathy2007

    • Author(s)
      Asaba K, Tojo A, Onozato ML, Goto A,Fujita T.
    • Journal Title

      J Cardiovasc Pharmacol 49(1)

      Pages: 13-19

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual blockade ofaldosterone and angiotensin II additively suppresses TGF-b and NADPHoxidase in the hypertensive kidney2007

    • Author(s)
      Onozato ML, Tojo A, Kobayashi N, Goto A, Matsuoka H, Fujita T.
    • Journal Title

      Nephrol Dial Transplant 22

      Pages: 1314-1322

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppressingrenal NADPH oxidase to treat diabetic nephropathy2007

    • Author(s)
      Tojo A, Asaba K. Onozato ML.
    • Journal Title

      Expert Opin Ther Targets 11(8)

      Pages: 1011-1018

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-carbonic anhydrase II antibody inautoimmune pancreatitis andtubulointerstitial nephritis2007

    • Author(s)
      Nishi H, Tojo A, Onozato ML, Jimbo R,Nangaku M, Uozaki H, Hirano K, Isayama H,Omata M, Kaname S, Fujita T.
    • Journal Title

      Nephrol Dial Transplant 22(4)

      Pages: 1273-1275

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Mouse Organic Anion Transporter 3(mOat3) as a Basolateral ProstaglandinE(2) Transport Pathway2007

    • Author(s)
      Nilwarangkoon S, Anzai N, Shiraya K, YuE, Islam R, Cha SH, Onozato ML, Miura D,Jutabha P, Tojo A, Kanai Y, Endou H.
    • Journal Title

      J Pharmacol Sci 103(1)

      Pages: 48-55

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-Specific Regulation by NG-NG-Dimethy larginine Dimethy laminohy drolase of Rat Serum Asymmetric Dimethy larginine and Vascular Endothelium-Derived Relaxing Factor/NO.2007

    • Author(s)
      Wang D, Gill PS, Chabrashvili C, Onozato ML, Raggio J, Mendonca M, Dennehy K, Li M, Modlinger P, Leiper J, Vallance P, Adler O, Leone A, Tojo A, Welch WJ, Wilcox CS
    • Journal Title

      Circ Res 101(6)

      Pages: 627-635

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Double-edged action of SOD mimetic in diabetic nephropathy.2007

    • Author(s)
      Asaba K, Tojo A, Onozato ML, Goto A, Fujita T.
    • Journal Title

      J Cardiovasc Pharmacol 49(1)

      Pages: 13-19

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual blockade of aldosterone and angiotensin II additively suppresses TGF-β and NADPH oxidase in the hypertensive kidney.2007

    • Author(s)
      Onozato ML, Tojo A, Kobayashi N, Goto A, Matsuoka H, Fujita T
    • Journal Title

      Nephrol Dial Transplant 22

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressing renal NADPH oxidase to treat diabetic nephropathy.2007

    • Author(s)
      Onozato ML, Tojo A, Asaba K
    • Journal Title

      Expert Opin Ther Targets. 11(8)

      Pages: 1011-1018

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Albumin handling along the nephron: Mechanism of proteinuria2008

    • Author(s)
      Tojo A, Kinugasa S, Onozato ML, Miyazaki H, Asaba K, Fujita T
    • Organizer
      The 9th Asian-Pacific Microscopy Conference
    • Place of Presentation
      Jeju,Korea
    • Year and Date
      2008-11-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] ラット糸球体における2nmgold標識アルブミンの濾過経路の検討2008

    • Author(s)
      衣笠哲史、藤乗嗣泰、小野里マリステラリカ、藤田敏郎
    • Organizer
      第40回日本臨床分子形態学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2008-10-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] L-07 Recent Progress of FunctionalMorphology of the Kidney.Albumin handling along the nephron : Mechanism of proteinuria2008

    • Author(s)
      Tojo A, Kinugasa S, Onozato ML, MiyazakiH, Asaba K, Fujita T.
    • Organizer
      The 9^<th> Asian-Pacific Microscopy Conference
    • Place of Presentation
      Jeju, Korea
    • Related Report
      2008 Final Research Report
  • [Presentation] 金粒子標識アルブミンとFITC標識アルブミンを用いた糸球体蛋白濾過の検討2008

    • Author(s)
      藤乗嗣泰, 小野里マリステラリカ, 浅羽研介, 衣笠哲史, 藤田敏郎
    • Organizer
      第51回日本腎臓学会学術総会
    • Place of Presentation
      福岡
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] ラット糸球体における2nm gold標識アルブミンの濾過経路の検討2008

    • Author(s)
      衣笠哲史, 藤乗嗣泰, 小野里マリステラリカ, 藤田敏郎
    • Organizer
      第40回日本臨床分子形態学会総会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2008 Final Research Report
  • [Presentation] Expression of DDAH and PRMT isoforms in diabetic rat kidney; effects of ARB.2007

    • Author(s)
      M. L. Onozato, A. Tojo, J. Leiper, T. Fujita, C. S. Wilcox.
    • Organizer
      The World Congress of Nephrology 2007
    • Place of Presentation
      Rio de Janeiro, Brazil
    • Year and Date
      2007-04-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] M-PO761 Expression of DDAH and PRMTisoforms in diabetic rat kidney ; effects ofARB2007

    • Author(s)
      Onozato ML, Tojo A, Leiper J, Fujita T, Wilcox CS.
    • Organizer
      The World Congress of Nephrology 2007
    • Place of Presentation
      Rio de Janeiro, Brazil
    • Related Report
      2008 Final Research Report
  • [Presentation] [SA-PO277] Role of Podocyte NADPH Oxidasein Proteinuria in Experimental and HumanNephrotic Syndrome2007

    • Author(s)
      Tojo A, Onozato ML, Kitiyakara C, Chalermsanyakorn P, Karnsombut P, Pinpradap K, Wilcox CS, Fujita T.
    • Organizer
      The American Society of Nephrology 40thAnnual Meeting
    • Place of Presentation
      San Francisco, CA, U.S.A
    • Related Report
      2008 Final Research Report
  • [Presentation] [SA-PO988] Comparison of Effects ofAngiotensin Blockade, Prednisolone orAnti-Platelet Drugs in IgA Nephropathy2007

    • Author(s)
      Asaba K, Tojo A, Onozato ML, Kimura K, GotoA, Fujita T.
    • Organizer
      The American Society of Nephrology 40thAnnual Meeting
    • Place of Presentation
      San Francisco, CA, U.S.A
    • Related Report
      2008 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi