• 研究課題をさがす
  • 研究者をさがす
  • KAKENの使い方
  1. 課題ページに戻る

2019 年度 実施状況報告書

Pyridoxamine could be a candidate drug for Parkinson`s disease: Mechanistic study to reduce dopamine-induced toxicity

研究課題

研究課題/領域番号 19K07187
研究機関東北大学

研究代表者

李 宣和  東北大学, 薬学研究科, 准教授 (60519776)

研究分担者 大江 知行  東北大学, 薬学研究科, 教授 (10203712)
研究期間 (年度) 2019-04-01 – 2022-03-31
キーワードPyridoxamine / Dopamine / Parkinson`s disease / Oxidative stress
研究実績の概要

Characterization of a pyridoxamine (PM)-dopamine (DA) adduct:
1. In the reaction of DA and PM, the (pyridoxal) PL-DA adduct was formed together with PL. The adduct corresponded to PL+DA-H2O was also produced in the reaction of DA and PL. Its structure was characterized to be a 1-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl-1,2,3,4-tetrahydroisoquinoline-6,7-diol formed through a Schiff base by MS/MS, UV, and NMR analyses.
2. Based on the results from the reaction of DA analogs and PM, the mechanism for the formation of PL-DA adduct was proposed. Thus, DA initially oxidizes to DA quinone (DAQ), which reacts with PM to produce PL after hydrolysis. PL then reacts with DA to form PL-DA adduct.
3. As the PM concentration increased, dose-dependent elevation of a PL-DA adduct was observed.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

As planned, DA was allowed to react with PM and the adduct (PL+DA-H2O) was characterized by MS/MS, UV, and NMR analyses. The mechanism for the formation of adduct was also proposed based on the reaction of DA analogs and PM. Dose-dependent elevation of a PL-DA adduct was observed. Therefore, PM could inhibit DA-induced neurotoxicity by directly scavenging DAQ.

今後の研究の推進方策

Investigation of the inhibition effects of PM:
1. Cysteine will be allowed to react with DA in the presence of PM.
2. Time- and concentration-dependent inhibition effects of PM will be investigated by monitoring the formations of 5S-cysteinyl-DA and a PM-DA adduct.

  • 研究成果

    (10件)

すべて 2019 その他

すべて 雑誌論文 (2件) (うち査読あり 2件) 学会発表 (5件) (うち国際学会 1件、 招待講演 1件) 備考 (3件)

  • [雑誌論文] Angiotensin II-induced oxidative stress in human endothelial cells: Modification of cellular molecules through lipid peroxidation2019

    • 著者名/発表者名
      Seon Hwa Lee, Shuhei Fujioka, Ryo Takahashi, and Tomoyuki Oe
    • 雑誌名

      Chemical Research in Toxicology

      巻: 32 ページ: 1412-1422

    • DOI

      10.1021/acs.chemrestox. 9b00110

    • 査読あり
  • [雑誌論文] LC-MS analysis of N-acetyl-p-benzoquinone imine-adducts of glutathione, cysteine, N-acetylcysteine, and albumin in a plasma sample: A case study from a patient with a rare acetaminophen-induced acute swelling rash2019

    • 著者名/発表者名
      Masashi Ozawa, Takashi Kubo, Seon Hwa Lee, and Tomoyuki Oe
    • 雑誌名

      The Journal of Toxicological Sciences

      巻: 44 ページ: 559-563

    • DOI

      10.2131/jts.44.559

    • 査読あり
  • [学会発表] 神経毒性を有するドパミン酸化体のピリドキサミンによる捕捉:LC-MSによる反応メカニズム解析2019

    • 著者名/発表者名
      松本直也、李宣和、大江知行
    • 学会等名
      みちのく分析科学シンポジウム2019
  • [学会発表] 過酸化脂質由来のインスリン抵抗性発現機構の解明2019

    • 著者名/発表者名
      筒井瑞紀、松永淳、李宣和、大江知行
    • 学会等名
      みちのく分析科学シンポジウム2019
  • [学会発表] Pyridoxamine as a potential scavenger of neurotoxic dopamine quinone2019

    • 著者名/発表者名
      Naoya Matsumoto, Seon Hwa Lee, Tomoyuki Oe
    • 学会等名
      2019年度 化学系学協会東北大会
  • [学会発表] Lipid hydroperoxide-derived insulin resistance in L6 skeletal muscle cells2019

    • 著者名/発表者名
      Mizuki Tsutsui, Atsushi Matsunaga, Seon Hwa Lee, Tomoyuki Oe
    • 学会等名
      2019年度 化学系学協会東北大会
  • [学会発表] Alternative approach for biomarker discovery through chemical modificomics2019

    • 著者名/発表者名
      Seon Hwa Lee
    • 学会等名
      2nd Tohoku University-Sichuan University Pharmaceutical Sciences Collaboration Symposium
    • 国際学会 / 招待講演
  • [備考] researchmap マイポータル

    • URL

      https://researchmap.jp/LSH6835

  • [備考] 東北大学大学院薬学研究科臨床分析化学分野ホームページ

    • URL

      http://www.pharm.tohoku.ac.jp/~bunseki/bunseki.html

  • [備考] 東北大学研究者紹介

    • URL

      http://db.tohoku.ac.jp/whois/detail/a63434da0ba1befd3ff395e655af195e.html

URL: 

公開日: 2021-01-27  

サービス概要 検索マニュアル よくある質問 お知らせ 利用規程 科研費による研究の帰属

Powered by NII kakenhi