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Lipid hydroperoxide-derived modifications to pyridoxamine: a novel biomarker of oxidative stress

Research Project

Project/Area Number 16K08391
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

Lee Seon Hwa  東北大学, 薬学研究科, 助教 (60519776)

Co-Investigator(Kenkyū-buntansha) 大江 知行  東北大学, 薬学研究科, 教授 (10203712)
佐藤 涼  東北大学, 薬学研究科, 助教 (20757166)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsOxidative stress, / Lipid peroxidation, / Pyridoxamine, / Mass spectrometry, / Protein modification / Chemical modification, / Mass spectrometry / Oxidative stress / Lipid peroxidation / Pyridoxamine / 酸化ストレス / 内因性ピリドキサミン / 化学修飾
Outline of Final Research Achievements

Pyridoxamine (PM) is a drug candidate for various chronic diseases because it can inhibit advanced glycation end product formation. PM might therefore prevent protein damage from lipid hydroperoxide-derived aldehydes 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2(E)-nonenal (HNE). Upon reaction with PM, ONE and HNE yielded an identical product containing a pyrrole ring, which structure was characterized by LC-MS and NMR. When human serum albumin (HSA) was reacted with a linoleic acid hydroperoxide, ONE modified more residues than did HNE. Upon treatment with PM, the formation of ONE-modified HSA peptides, but not of HNE-modified peptides, was reduced. Concomitantly, PM-ONE adducts increased in a dose-dependent manner. The inhibition effect of PM was confirmed in the cell system subjected to oxidative stress. Therefore, PM can inhibit lipid hydroperoxide-derived damage to proteins by trapping ONE preferentially, and the resulting PM-ONE adducts can be used as a dosimeter for ONE production.

Academic Significance and Societal Importance of the Research Achievements

今回、過酸化脂質由来の求電子性アルデヒド化合物とPMの反応機構、反応生成物、および修飾阻害効果を精査した。これらの知見からPMは、糖尿病のみならず、酸化・脂質化の関与する様々な慢性疾患(高脂血症、老化など)さらには生活習慣(喫煙、飲酒など)によるタンパク質ダメージの抑制効果も期待される。同様にPMは、化学発癌や薬物毒性などの原因となる求電子性代謝物の捕捉を通して、タンパク質・DNA修飾を抑制する効果も期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (4 results)

  • [Journal Article] Inhibition effect of pyridoxamine on lipid hydroperoxide-derived modifications to human serum albumin2018

    • Author(s)
      Seon Hwa Lee, Atsushi Matsunaga, Tomoyuki Oe
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 4 Pages: e0196050-e0196050

    • DOI

      10.1371/journal.pone.0196050

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomimetic trapping cocktail to screen reactive metabolites: use of an amino acid and DNA motif mixture as light/heavy isotope pairs differing in mass shift2018

    • Author(s)
      Shuto Hosaka、Takuto Honda、Seon Hwa Lee、Tomoyuki Oe
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 410 Issue: 16 Pages: 3847-3857

    • DOI

      10.1007/s00216-018-1057-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imidazole dipeptides can quench toxic 4-oxo-2(E)-nonenal: Molecular mechanism and mass spectrometric characterization of the reaction products2018

    • Author(s)
      Fumiya Tatsuno, Fumiya Tatsuno, Seon Hwa Lee, Tomoyuki Oe
    • Journal Title

      Journal of Peptide Science

      Volume: 8-9 Issue: 8-9

    • DOI

      10.1002/psc.3097

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stable isotope labeling by fatty acids in cell culture (SILFAC) coupled with isotope pattern dependent mass spectrometry for global screening of lipid hydroperoxide-mediated protein modifications2017

    • Author(s)
      Ryo Takahashi, Shuhei Fujioka, Tomoyuki Oe, Seon Hwa Lee
    • Journal Title

      Journal of Proteomics

      Volume: 166 Pages: 101-114

    • DOI

      10.1016/j.jprot.2017.07.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oxidative stress-mediated N-terminal protein modifications and MS-based approaches for N-terminal proteomics2016

    • Author(s)
      Seon Hwa LEE and Tomoyuki OE
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 31 Issue: 1 Pages: 27-34

    • DOI

      10.1016/j.dmpk.2015.12.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] UV irradiation-induced methionine oxidation in human skin keratins: Mass spectrometry-based non-invasive proteomic analysis.2016

    • Author(s)
      Seon Hwa LEE, Keita MATSUSHIMA, Kohei MIYAMOTO, and Tomoyuki OE
    • Journal Title

      Journal of Proteomics

      Volume: 133 Pages: 54-65

    • DOI

      10.1016/j.jprot.2015.11.026

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mass spectrometry data from proteomic analysis of human skin keratins after exposure to UV radiation.2016

    • Author(s)
      Seon Hwa LEE, Keita MATSUSHIMA, Kohei MIYAMOTO, and Tomoyuki OE
    • Journal Title

      Data in Brief

      Volume: 7 Pages: 100-106

    • DOI

      10.1016/j.dib.2016.02.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 基礎講座:生体分子の構造解析・定性の基礎2018

    • Author(s)
      李宣和
    • Organizer
      第45回BMSコンファレンス
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 血漿中N末端α-ケトアミド型アンジオテンシン類のLC/ESI-SRM/MS法の開発2018

    • Author(s)
      池田真人、横田涼、李宣和、大江知行
    • Organizer
      日本分析化学会第67年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂質過酸化物由来のタンパク質修飾スクリーニング法に関する研究:安定同位元素標識脂質と同位体パターン特異的MS/MS解析2018

    • Author(s)
      越遼貴、高橋亮、李宣和、大江知行
    • Organizer
      日本分析化学会第67年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ピリドキサミンによるドパミン酸化体捕捉メカニズムの研究2018

    • Author(s)
      松本直也、景賢淑、李宣和、大江知行
    • Organizer
      第57回 日本薬学会東北支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 過酸化脂質由来のインスリン抵抗性発現機構の解明:細胞中IRS1の化学修飾評価系構築に関する基礎検討2018

    • Author(s)
      筒井瑞紀、松永淳、李宣和、大江知行
    • Organizer
      第57回 日本薬学会東北支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Screening of lipid hydroperoxide-mediated protein modification using stable isotope labeling by fatty acids in cell culture (SILFAC) coupled with isotope pattern dependent scan2017

    • Author(s)
      Seon Hwa Lee
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] N末端ピルビン酸アミド型アンジオテンシンの同位体希釈LC/ESI-SRM/MS分析2017

    • Author(s)
      池田真人、横田涼、大江知行、李宣和
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] On-tape消化法を用いるヒト表皮ケラチン上の化学修飾スクリーニング2017

    • Author(s)
      川瀬士瑛、廣嶋佑亮、大江知行、李宣和
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト内皮細胞中のアンジオテンシンII誘発脂質過酸化のLC/ESI-MS解析2017

    • Author(s)
      藤岡修平、髙橋亮、大江知行、李宣和
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Inhibition of lipid hydroperoxide-derived protein modifications by pyridoxamine2017

    • Author(s)
      松永淳、景賢淑、李宣和、大江知行
    • Organizer
      日本分析化学会東北支部若手交流会
    • Related Report
      2017 Research-status Report
  • [Presentation] LC/ESI-SRM/MSを用いた血漿中N末端α-ケトアミド型アンジオテンシン類定量法の開発2017

    • Author(s)
      池田真人、横田涼、李宣和、大江知行
    • Organizer
      日本分析化学会東北支部若手交流会
    • Related Report
      2017 Research-status Report
  • [Presentation] 求電子性薬物代謝物とDNA塩基の反応に関する基礎的研究2017

    • Author(s)
      中川智恵、李 宣和、大江知行
    • Organizer
      第56回日本薬学会東北支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] LC/ESI-SRM/MSを用いたN末端α-ケトアミド型アンジオテンシン類分析法の開発2017

    • Author(s)
      池田 真人、横田 涼、李 宣和、大江知行
    • Organizer
      新アミノ酸分析研究会第7回学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] タンパク質・ペプチドの新規N末端修飾分子メカニズムと臨床的意義2017

    • Author(s)
      大江知行、李宣和
    • Organizer
      新アミノ酸分析研究会第7回学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] Pyridoxamine inhibits lipid hydroperoxide-derived modifications to human serum albumin2016

    • Author(s)
      Atsushi Matsunaga, Hyunsook Kyung, Tomoyuki Oe, Seon Hwa Lee
    • Organizer
      新アミノ酸分析研究会 第6回学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Inhibition of lipid hydroperoxide-derived protein damages by pyridoxamine2016

    • Author(s)
      Seon Hwa Lee, Atsushi Matsunaga, Hyunsook Kyung, Tomoyuki Oe
    • Organizer
      KSMS Summer Conference
    • Place of Presentation
      Gyeongju, Korea
    • Year and Date
      2016-08-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 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

    • Related Report
      2018 Annual Research Report 2017 Research-status Report 2016 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/read0140803

    • Related Report
      2018 Annual Research Report
  • [Remarks] ORCID iD

    • URL

      https://orcid.org/0000-0003-1095-5516

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 東北大学研究者紹介

    • URL

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

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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