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

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Okayama 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
• 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

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.

Research Products

• [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
  • 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
  • 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
  • Year and Date: 20110325-20110328
• [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
  • Year and Date: 20101207-20101210
• [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
  • Year and Date: 20090327-20090329
• [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
  • Year and Date: 20090101-20090103