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2004 Fiscal Year Final Research Report Summary

Protective role of red blood cells PAF-acetylhydrolase against oxidative siess

Research Project

Project/Area Number 15590069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTeikyo University

Principal Investigator

KARASAWA Ken  Teikyo University, Faculty of pharmaceutical Sciences, Associated professor, 薬学部, 助教授 (50186029)

Project Period (FY) 2003 – 2004
KeywordsPlatelet-activating factor (PAF) / PAF-acetylhydrolase / Red blood cells / Oxidative stress / Oxidized liuids
Research Abstract

Three kinds of subtypes have been identified as PAF-acetylhydrolase (PAF-AH) which degrades PAF ; mediator of inflammation and allergy. Those consist of plasma-type, distributed in body fluids such as plasma, and intracellular type I and type II. Type I PAF-AH forms oligomer consisting of catalytic subunits termed α_1 or α_2. In the human blood, 70 % of enzyme activity is detected in plasma, while 30 % of enzyme activity is detected in red blood cells. Total enzyme activity of white blood cells such as polymorphonuclear leukocytes and platelets was less than 1 %. Despite high occupancy of enzyme activity, subtype of this enzyme and physiological role remain unknown. In this study, enzyme purification was undertaken from easily available pig blood. As a result, it was clarified that pig red blood cells contained α_1/ α_2 heterodimer and α2/α2 homodimer. Although ai subunit is highly expressed in fetal brain, expression of this subunit is very low in the adult except spermatogonium. By contrast, white blood cells such as polymorphonuclear leukocytes and platelets contained α_2/α_2 homodimer alone. This fact suggests that this subunit plays an important role in regulation of red blood cells function. In addition, Western blotting analysis using specific antibodies to these subunits showed that human red blood cells contained α_1/α_2 heterodimer and α_2/α_2 homodimer, as well as human red blood cells.
Since red blood cells do not produce PAF and lack PAF receptor, physiological substrate towards this enzyme is not thought to be PAR Thus, we added recombinant PAF-AH to the lipids extracted from red blood cells membranes and analyzed the lipid constituents by mass-spectrometry. As a result, it was shown that recombinant PAF-AH degraded oxidatively modified lipids of the red blood cells membranes exposed by Cu^<2+> as the substrates.

  • Research Products

    (6 results)

All 2003

All Journal Article (6 results)

  • [Journal Article] Regulation of Activities of CDP-choline:1-0-alkyl-2-acetyl-sn-glycerol Cholinephosphotransferase (AAG-CPT), an Enzyme Responsible for de novo Synthesis of Platelet-Activating Factor (PAF), by Membrane Phospholipids.2003

    • Author(s)
      Noriko Satoh, Ayako Harada, Kazuaki Yokoyama, Ken Karasawa, Keizo Inoue, Morio Setaka
    • Journal Title

      J.Health.Sci 49

      Pages: 13-21

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Plasma Platelet activating Factor-acetylhydrilase (PAF-AH)2003

    • Author(s)
      Ken Karasawa, Ayako Harada, Noriko Satoh, Keizo Inoue, Morio Setaka
    • Journal Title

      Prog.Lipid.Res. 42

      Pages: 93-114

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human Plasma Platelet-activating Factor Acetylhydrolase Binds to All the Murine Lipoproteins, Conforring Protection against Oxidetive Stress.2003

    • Author(s)
      Hiroshi Noto, Masumi Hara, Ken Karasawa, Naoyuki Iso-O, Hiroaki Satoh, Masako Toga, Yoshiaki Hashimoto, Yoshiji Yamada, Tetsuya Kosaka, Mitsunobu Kawamura, Satoshi, Kimura, Kazuhisa Tsukamoto
    • Journal Title

      Artherioseler.Thromb, Vasc.Biol. 23

      Pages: 829-835

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of Activities of CDP-choline : 1 -O-alkyl-2-acetyl-sn-glycerol Cholinephosphotransferase (AAG-CPT), an Enzyme Responsible for de novo Synthesis of Platelet-activating Factor (PAF), by Membrane Phospholipids.2003

    • Author(s)
      Noriko Satoh, Ayako Harada, Kazuaki Yokoyama, Ken Karasawa, Keizo Inoue, Mono Setaka
    • Journal Title

      J.Health.Sci 49

      Pages: 13-21

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Plasma Platelet-activating Factor-acetylhydrolase (PAF-AH).2003

    • Author(s)
      Ken Karasawa, Ayako Harada, Noriko Satoh, Keizo Inoue, Morio Setaka
    • Journal Title

      Prog.Lipid.Res. 42

      Pages: 93-114

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human Plasma Platelet-activating Factor Acetylhydrolase Binds to All the Murine Lipoproteins, Conferring Protection against Oxidative Stress.2003

    • Author(s)
      Hiroshi Noto, Masumi Hara, Ken Karasawa, Naoyuki Iso-O, Hiroaki Satoh, Masako Toga, Yoshiaki Hashimoto, Yoshiji Yamada, Tetsuya Kosaka, Mitsunobu Kawamura, Satoshi, Kimura., Kazuhisa Tsukamoto
    • Journal Title

      Artherioscler.Thromb.Vasc.Biol. 23

      Pages: 829-835

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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