Role of DDAH, a metabolizing enzyme for endogenous NO inhibitor ADMA,in diabetic nephropathy : its therapeutic application
| Project/Area Number |
19590938
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TOJO Akihiro The University of Tokyo, 医学部・附属病院, 講師 (50292917)
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| Project Period (FY) |
2007 – 2008
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| Project Status |
Completed (Fiscal Year 2008)
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| 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)
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| Keywords | 糖尿病性腎症 / ADMA / DDAH / nitric oxide / eNOS / 酸化ストレス / angiotensin receptor blocker |
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| 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。
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Report
(3 results)
Research Products
(34 results)
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[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.
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Journal Title
Cell Physiol Biochem 21(4)
Pages: 269-278
Related Report
Peer Reviewed
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[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.
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Journal Title
Circ Res 101(6)
Pages: 627-635
Related Report
Peer Reviewed
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[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.
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Journal Title
Nephrol Dial Transplant 22(4)
Pages: 1273-1275
Related Report
Peer Reviewed
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[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.
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Journal Title
J Pharmacol Sci 103(1)
Pages: 48-55
Related Report
Peer Reviewed
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[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
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Journal Title
Circ Res 101(6)
Pages: 627-635
Related Report
Peer Reviewed
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