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Study on Development of Bioregurative Substances Related with Generation and Elimination for Active Oxygen and Nitrogen Species.

Research Project

Project/Area Number 11672222
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

IKOTA Nobuo  National Institute of Radiological Sciences, 1st Research group, subgroup leader, 第一研究グループ, サブグループリーダー (80159649)

Co-Investigator(Kenkyū-buntansha) NAKAGAWA Hidehiko  National Institute of Radiological Sciences, 1st Research group, senior researcher, 第一研究グループ, 主任研究員 (80281674)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsreactive oxygen species / reactive nitrogen species / peroxynitrite / superoxide / hydroxyl radical / nitrotyrosine / spintrapping method / polyphenol / 抗酸化剤 / フラボノイド / ジチロシン
Research Abstract

Explorative study on scavenger for superoxide and hydroxyl radical, as reactive oxygen species, and peroxynitrite as reactive nitrogen species from natural producs and synthetic compounds was conducted. The scavenging abilities were estimated with ESR spin-trapping method using DMPO as spin trapping reagent for superoxide and hydroxyl radical, and with HPLC for peroxynitrite. Nitrating and oxidizing activities were estimated by the formation of 3-nitrotyrosine and dityrosine with a HPLC-UV-fluorescence detector system. The compounds used in this study were chalcon, 5-methoxytryptaminyl caffeic acid amide, extract from apple, RK-160 and RK-02B(extract from licorice), and trolox(synthetic aqueous soluble vitamin E derivative). Superoxide was generated from hypoxantine-xantine oxidase system and hydroxyl radical was generated from Cu(en)_2-H_2O_2 system. Peroxynitrite was prepared from ozone and sodium azide. Chalcon, extract from apple, and RK02B showed high scanenging ability against superoxide, hydroxyl radical, and peroxynitrite.
During the study on scavenger for peroxynitrite, we have found that 5-methoxytryptamine and a-lipoic acid only inhibited the nitration reaction, and enhanced the formation of an oxidation product. This is important evidence that there are different intermediates in the nitrating and oxidizing reactions of L-tyrosine by peroxynitrite such as caged dipolar form [ONO^+ ……^-ON].

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (25 results)

All 2001 2000 1999 Other

All Journal Article (15 results) Book (1 results) Publications (9 results)

  • [Journal Article] Induction of Superoxide in Glioma Cell Line U87 Stimulated with Lipopolysaccharide and Interferon Gamma : ESR Using a New Flow-type Quartz Cell.2001

    • Author(s)
      Hidehiko Nakagawa, Nobuo Ikota, et al.
    • Journal Title

      FEBS Lett. 471

      Pages: 753-765

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Synthesis of N-Methyl-3-(1-Hydroxy-5-[^<123>I]Iodopent-4-enyl)-4-Acetoxypiperidine, A Novel Candidate of Acetylcholinesterase Activity Imaging Agent2001

    • Author(s)
      Takao Ueda, Toshiaki Irie, Nobuo Ikota, et al.
    • Journal Title

      J.Labelled Cpd.Radiopharm. 43

      Pages: 753-765

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Dose and time dependence of radiation-induced nitric oxide formation in as quantified with electron paramagnetic resonance.2001

    • Author(s)
      H.Nakagawa, N.Ikota, T.Ozawat, Y.Kotake
    • Journal Title

      Nitric Oxide : Biology and Chemistry (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Synthesis of Piperidinyl and Pyrrolidinyl Butyrates for In Vivo measurement of Cerebral Butyrylcholinesterase Activity.2001

    • Author(s)
      Kikuchi, Tatsuya, Fukushi, Kiyoshi, Ikota, Nobuo, Ueda, Takao, Nagatsuka, Shin-ichiro, Arano, Yasushi, Irie, Toshiaki
    • Journal Title

      J Labelled Cpd.Radiopharm. 43

      Pages: 753-765

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Dose and time dependence of radiation-induced nitric oxide formation in as quantified with electron paramagnetic resonance.2001

    • Author(s)
      H.Nakagawa, N.Ikota, T.Ozawat, Y.Kotake
    • Journal Title

      Nitric Oxide : Biology and Chemistry. 5

      Pages: 47-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Scavengers for Peroxynitrite : Inhibition of Tyrosine Nitration and Oxidation with Tryptamine Derivatives, α-Lipoic Acid and Synthetic Compounds2000

    • Author(s)
      Nakagawa, H., Ikota, N., et al.
    • Journal Title

      Chem.Pharm.Bull. 48

      Pages: 261-265

    • NAID

      110003635439

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Scavengers for Peroxynitrite : Inhibition of Tyrosine Nitration and Oxidation with Tryptamine Derivatives, α-Lipoic Acid and Synthetic Compounds2000

    • Author(s)
      Hidehiko Nakagawa, Erika Sumiki, Mitsuko Takusagawa, Nobuo Ikota, Yoshikazu Matsushima, Toshihiko Ozawa
    • Journal Title

      Chem.Pharm.Bull. 48

      Pages: 261-265

    • NAID

      110003635439

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Induction of Superoxide in Glioma Cell Line U87 Stimulated with Lipopolysaccharide and Interferon Gamma : ESR Using a New Flow-type Quartz Cell.2000

    • Author(s)
      Hidehiko Nakagawa, Takashi Moritake, Koji Tsuboi, Nobuo Ikota, Toshihiko Ozawa
    • Journal Title

      FEBS Lett. 471

      Pages: 187-190

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Synthesis of N-Methyl-3-(1-Hydroxy-5-[^<123>I]Iodopent-4-enyl)-4-Acetoxypiperidine, A Novel Candidate of Acetylcholinesterase Activity Imaging Agent.2000

    • Author(s)
      Takao Ueda, Toshiaki Irie, Kiyoshi Fukushi, Nobuo Ikota, Keizo Takatoku, Isamu Yomoda, Shin-ichiro Nagatsuka
    • Journal Title

      J Labelled Cpd.Radiopharm. 43

      Pages: 753-765

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Enogenous and New Synthetic Antioxidants for Peroxynitrite : selctive Inhibitory Effect of 5-Methoxytryptamine and α-Lipic Acid on Tyrosine Nitration by Peroxynitrite.1999

    • Author(s)
      Nakagawa, H., Ikota, N.et al.
    • Journal Title

      Antioxidants and Redox Signaling 1

      Pages: 239-244

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Isolation and Cloning of Rat Poly(ADP-ribose) Glycohydrolase : Presence of a Potential Nuclear Export Signal Conserved in Mammalian Orthologs.1999

    • Author(s)
      Shimokawa T., Masutani, M., Ikota, N., Sugimura, T.et al.
    • Journal Title

      J.Biochemistry 128

      Pages: 748-755

    • NAID

      10005858785

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] A New Synthesis of All Four Stereoisomers of 2-(2,3-Dihydroxypropyl)piperidines via Iterative Asymmetric Dihydroxylation to Cause Enantiomeric Enhancement. Application to Asymmetric Synthesis of Naturally Occurring Piperidine Related Alkaloids.1999

    • Author(s)
      Takahata, H., Kubota, M., Ikota, N.
    • Journal Title

      J.Org.Chem. 1

      Pages: 8594-8601

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Endogenous and new Synthetic Antioxidants for Peroxynitrite : Selctive Inhibitory Effect of 5-Methoxytryptamine and Lipoic Acid on Tyrosine Nitration by Peroxynitrite.1999

    • Author(s)
      Nakagawa, H., Sumiki, E., Ikota, N., Matsushima, Y., Ozawa, T.
    • Journal Title

      Antioxidants and Redox Signaling 1

      Pages: 239-244

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Isolation and Cloning of Rat Poly(ADP-ribose) Glycohydrolase : Presence of a Potential Nuclear Export Signal Conserved in Mammalian Orthologs.1999

    • Author(s)
      Takashi Shimokawa, Mitsuko Masutani, Shingo Nagasawa, Tadashige Nozaki, Nobuo lkota, Yoshiro Aoki, Hitoshi Nakagama, Takashi Sugimura.
    • Journal Title

      J Biochemistry 126

      Pages: 748-755

    • NAID

      10005858785

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] A New Synthesis of All Four Stereoisomers of 2-(2,3-Dihydroxypropyl)piperidines via Iterative Asymmetric Dihydroxylation to Cause Enantiomeric Enhancement. Application to Asymmetric Synthesis of Naturally Occurring Piperidine Related Alkaloids.1999

    • Author(s)
      Hiroki Takahata, Minoru Kubota, Nobuo Ikota
    • Journal Title

      J Org.Chem. 64

      Pages: 8594-8601

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Book] 生体内一酸化窒素(NO)実験プロトコール2000

    • Author(s)
      中川秀彦, 小澤俊彦, 伊古田暢夫 (分担), 吉村哲彦編
    • Total Pages
      288
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa,H.,Sumiki,E.,Takusagawa,M.,Ikota,N.,Matsushima,Y.,and Ozawa,T.: "Scavengers for Peroxynitrite : Inhibition of Tyrosine Nitration and Oxidation with Tryptamine Derivatives, α-Lipoic Acid and Synthetic Compounds"Chem.Pharm.Bull.. 48. 261-265 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hidehiko Nakagawa,Takashi Moritake,Koji Tsuboi,Nobuo Ikota and Toshihiko Ozawa: "Induction of Superoxide in Glioma Cell Line U87 Stimulated with Lipopolysaccharide and Interferon Gamma : ESR Using a New Flow-type Quartz Cell."FEBS Lett.. 471. 187-190 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takao Ueda,Toshiaki Irie,Kiyoshi Fukushi,Nobuo Ikota,Keizo Takatoku,Isamu Yomoda,Shinichiro Nagatsuka: "Synthesis of N-Methyl-3-(1-Hydroxy-5-[^<123>I]Iodopent-4-enyl)-4-Acetoxypiperidine, A Novel Candidate of Acetylcholinesterase Activity Imaging Agent"J.Labelled Cpd.Radiopharm.. 43. 753-765 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kikuchi Tatsuya,Fukushi Kiyoshi,Ikota,Nobuo,Ueda,Takao,Nagatsuka,Shin-ichiro,Arano,Yasushi,Irie,Toshiaki,1: "Synthesis of Piperidinyl and Pyrrolidinyl Butyrates for In Vivo measurement of Cerebral Butyrylcholine sterase Activity."J.Labelled Cpd.Radiopharm.. 43(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Nakagawa,N.Ikota,and T.Ozawat,Y.Kotake: "L-Arginine dependent nitric oxide formation in mice following exposure to ionizin radiation as quantified by electron paramagnetic resonance"Nitric Oxide : Biology and Chemistry. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa H.,Sumiki E.,Ikota N.,Matsushima Y.,Ozawa T.: "Enogenous and New Synthetic Antioxidants for Peroxynitrite : selctive Inhibitory Effect of 5-Methoxytryptamine and Lipic Acid on Tyrosine Nitration by Peroxynitrite"Antioxidants and Redox Signaling. 1. 239-244 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimokawa T.,Masutani M.,Nagasawa S.,Nozaki T.,Ikota N.,Aoki Y.,Nakagama H.,Sugimura T.: "Isolation and Cloning of Rat Poly(ADP-ribose)Glycohydrolase : Presence of a Potential Nuclear Export Signal Conserved in Mammalian Orthologs"J.Biochmistry. 126. 748-755 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahata H.,Kubota M.,Ikota N.: "A New Synthesis of All Four Stereoisomers of 2-(2,3-Dihydroxypropyl)piperidines via Iterative Asymmetric Dihydroxylation to Cause Enantiomeric Enhancement. Application to Asymmetric Synthesis of Naturally Occurring Piperidine Related Alkaloids"J.Org.Chem.. 64. 8594-8601 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakagawa H.,Sumiki E.,Takusagawa M.,Ikota N.,Matsushima Y.and Ozawa T.: "Scavengers for Peroxynitrite : Inhibition of Tyrosine Nitration and Oxidation with Tryptamine Derivatives,a-Lipoic Acid and Synthetic Compounds"Chem.Pharm.Bull.. 48. 261-265 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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