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2007 Fiscal Year Final Research Report Summary

Construction of Hemoglobin-vesicle with long-term in vivo oxygen transporting ability

Research Project

Project/Area Number 18500368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionWaseda University

Principal Investigator

TAKEOKA Shinji  Waseda University, Faculty of Science and Engineering, Professor (20222094)

Project Period (FY) 2006 – 2007
KeywordsHemoglobin / Hemoglobin-vesicle / Artificial oxygen carrier / metHb formation / Tyrosine / Peroxidase / Hydrogen peroxide / Carbonylation
Research Abstract

The hemoglobin vesicles (HbV) encapsulating hemoglobin (Hb), which binds oxygen reversibly, in the phospholipid vesicle (liposome) function as an artificial oxygen carrier. However, Hb loses an oxygen binding capacity when central iron is oxidized from two valences to three (metHb formation). In this phenomenon, metHb formation (autoxidation) by one electron transfer from the central iron to the bound oxygen and the further metHb formation by the resulting reactive oxygen (peroxide) are taken place in a row. We have found out that a (metHb Hb/L-tyrosine) system eliminates peroxide promptly. In present study, it was confirmed that the hydrogen peroxide elimination system utilizing the peroxidase activity of metHb which uses L-tyrosine as a substrate was effective for suppression of metHb formation. Moreover, we confirmed the remarkable suppression of metHb formation of HbV which included this system in their inner aqueous phase, even if hydrogen peroxide were continuously added to the H … More bV dispersion. When the 20mL/kg of the HbV dispersion was administrated into rats, the half time of metHb formation in this HbV extended till 44 hours in comparison with 14 hours of the conventional HbV. Furthermore, from a novel screening method which measured the reaction rate of ferryl Hb radical with 14 kinds of candidate substances other than Tyr, we found that some derivatives which possesses indore rings such as tryptophane or carboxyl groups showed the suppressive effect higher than Tyr.
On the other hand, metHb formation caused from autoxidation does not occur for carbonyl Hb (HbCO). And if we use the phenomenon of the gradual conversion of HbCO into HbO_2 in blood circulation, we can maintain an oxygen carrying capacity by suppressing the metHb formation of HbV containing HbCO. In present study, we measured the change of the metHb formation rate of HbV containing HbCO and clarified that the rate of metHb from the remaining HbO_2 was the same in spite of the differed portion of HbCO. Therefore, it is suggested that gentle metHb formation system can be constructed in accompanied with the elimination of CO from HbCO. As mentioned above, if these dual approaches are paired, it is expected that the metHb formation of HbV can be effectively controlled by in vivo. Less

  • Research Products

    (15 results)

All 2008 2007 2006 2005 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Encapsulation of concentrated hemoglobin solution in phospholipid vesicles retards the reaction with NO, but not CO, by intracellular diffusion barrier2008

    • Author(s)
      Hiromi Sakai, Atsushi Sato, Kaoru Masuda, Shinji Takeoka, Eishun Tsuchida
    • Journal Title

      J.Biol.Chem. 283

      Pages: 1508-1517

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 血液の仕組みと人工血液(血液代替物)へのアプローチ2008

    • Author(s)
      武岡真司、岡村陽介
    • Journal Title

      化学と教育 56

      Pages: 260-263

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Science of Blood and Approach towards Artificial Blood(Blood Substitute)2008

    • Author(s)
      Shinji Takeoka, Yosuke Okamura
    • Journal Title

      Chemistry and Education 56

      Pages: 260-263

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Enzymatic elimination of hydrogen peroxide by a methemoglobin/L-tyrosine system2007

    • Author(s)
      Tomoyasu Atoji, Hirotaka Yatami, Motonari Aihara, Shinji Takeoka
    • Journal Title

      Art.Cells Blood Subs.Biotech. 35

      Pages: 555-567

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Enzymatic elimination of hydrogen peroxide by a methemoglobin/L-tyrosine system2007

    • Author(s)
      Tomoyasu Atoji, Hirotaka Yatami, Motonari Aihara, Shinji Takeoka
    • Journal Title

      Art.Cells Blood Subs.Biotech 35

      Pages: 555-567

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hemoglobin Vesicles Containing Methemoglobin and 1-Tyrosine to Suppress Methemoglobin Formation in Vitro and in Vivo2006

    • Author(s)
      Tomoyasu Atoji, Motonari Aihara, Hiromi Sakai, Eishun Tsuchida, Shinji Takeoka
    • Journal Title

      Bioconjugate Chemistry 17

      Pages: 1241-1245

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 「研究成果報告書概要(和文)」より2006

    • Author(s)
      本宮達也(監修)、武岡真司, 岡村陽介, 阿閉友保
    • Journal Title

      “ファイバー"スーパーバイオバイオメティクス~近未来の新技術創成~動く臓器としての血液に学ぶ-人工赤血球・人工血小板への挑戦-",((株)エヌ・ティー・エス)

      Pages: 453-457

  • [Journal Article] Fiber2006

    • Author(s)
      Tatsuya Motomiya(Supervisor), Shinji Takeoka, Yosuke Okamura, Tomoyasu Atoji
    • Journal Title

      Super Biomimetics, Creation of New Technology in Near Future, "Lean from Blood as a Moving Organ ; Challange to create artificial red blood cells and artificial platelets(NTS(Tokyo))

      Pages: 453-457

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] L-チロシンによるフェリルヘモグロビンラジカル還元反応の解析とヘモグロビン小胞体への応用2006

    • Author(s)
      阿閉友保, 谷田海博孝, 相原源就, 武岡真司, 土田英俊
    • Organizer
      第55回高分子学会年次大会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      20060500
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] L-チロシンによるフェリルヘモグロビン還元反応の解析(1)2006

    • Author(s)
      阿閉友保, 相原源就, 土田英俊, 武岡真司
    • Organizer
      日本化学会第86春季年会
    • Place of Presentation
      日本大学船橋キャンパス
    • Year and Date
      20060300
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] L-チロシンによるフェリルヘモグロビン還元反応の解析(2)2006

    • Author(s)
      谷田海博孝, 阿閉友保, 土田英俊, 武岡真司
    • Organizer
      日本化学会第86春季年会
    • Place of Presentation
      日本大学船橋キャンパス
    • Year and Date
      20060300
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Analysis of the reduction of ferryl Hemoglobin by L-tyrosine(1)2006

    • Author(s)
      Tomoyasu Atoji, Motonari Aihara, Eishun Tsuchida, Shinji Takeoka
    • Organizer
      The 83rd Spring Annual Meeting of the Chemical Society of Japan
    • Place of Presentation
      Nihon Univ.Funabashi
    • Year and Date
      20060300
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Analysis of the reduction of ferryl Hemoglobin by L-tyrosine(2)2006

    • Author(s)
      Hirotaka Yatami, Tomoyasu Atoji, Eishun Tsuchida, Shinji Takeoka
    • Organizer
      The 83rd Spring Annual Meeting of the Chemical Society of Japan
    • Place of Presentation
      Nihon Univ.Funabashi
    • Year and Date
      20060300
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Analysis of the reduction of ferryl hemoglobin radical by L-tyrosine and application in hemologbinvesicles2005

    • Author(s)
      Tomoyasu Atoji, Hirotaka Yatami, Motonari Aihara, Shinji Takeoka, Eishun Tsuchida
    • Organizer
      The 55th Annual Meeting, The Society of Polymer Science
    • Place of Presentation
      Nagoya Congress Center
    • Year and Date
      20050500
    • Description
      「研究成果報告書概要(欧文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.takeoka.biomed.sci.waseda.ac.jp/

URL: 

Published: 2011-06-18  

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