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2006 Fiscal Year Final Research Report Summary

Marignancy of cell-proliferative diseases by unusual production of phospholipid mediators in response to oxidative stress

Research Project

Project/Area Number 16390034
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

TOKUMURA Akira  The University of Tokushima, Graduate School, Institute of Health Sciences, Associate professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (00035560)

Co-Investigator(Kenkyū-buntansha) FUKUZAWA Kenji  The University of Tokushima, Graduate School, Institute of Health Sciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (90035551)
YAMANO Shuji  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (30166772)
Project Period (FY) 2004 – 2006
Keywordsoxidative stress / lysophospholipid / lysophospholipase D / lysophosphatidic acid / platelet activating factor / oxidized phospholipid / atherosclerosis / cancer metastasis
Research Abstract

First, we devised useful quantitative methods for primary (hydroperoxides) and secondary [platelet-activating factor (PAF)-like lipid] products of peroxidized phosphatidylcholines (PC). Using these methods, we found that three PAF-like lipids having a short chain acyl group were generated during incubation of human plasma with Cu^+ [dicarboxylate(DC)-containing PC > dicarboxylate semialdehyde(DCsa)-containing PC > monocarboxylate(MC)-containing PC]. The predominant PAF-like lipid in human plasma incubated with Fe^<2+> was MC-PC. A minor amount of DCsa-PC, but not DC-PC, was also detected. Both DC-PC and DCsa-PC stimulated the proliferation of human umbilical vein endothelial cells at concentrations less than 25 μM, but induced the apoptosis of the endothelial cells at higher concentrations.
We found that lysophospholipase D (lysoPLD) partially purified from human plasma and recombinant lysoPLD/autotaxin hydrolyzed PAF-like lipids and their deacylated product (lysophosphatidylcholine) in … More to phosphatidic acid having a short chain acyl group and lysophosphatidic acid that possess a potent cell-proliferative effect on various animal cells.
We devised a convenient assay for lysoPLD activity on a microplate reader. With use of the assay, we found that lysoPLD activities in sera from patients suffering from preeclamptia and preterm labor were higher than that observed for women under normal pregnancy, We also found that lysoPLD activities in peritoneal fluids from patients with ovarian cancer, cystadenoma, dermoid cyst and myoma uteri were higher than those for patients with other gynecological disease.
From these results, we suggested that increased oxidative stress in animal body caused peroxidation of PC in biomembranes and lipoproteins followed by the cleavage of C-C bond(s), generating PAF-like lipid. The PAF-like lipids and their deacylated product were then hydrolyzed by lysoPLD activity in various biological fluids into bioactive phosphatidic acid and lysophosphatidic acid. Our results indicate that high lysoPLD activity in the biological fluids from preeclamptic patients with injured vascular endothelium and patients with gynecological tumor might be a factor that could affect the malignancy of the diseases Less

  • Research Products

    (10 results)

All 2007 2006

All Journal Article (10 results)

  • [Journal Article] Movement of monoglyceridederived from hydrolysis of fluororescence-labeled lyso platelet-activating factor by lysophospholipase C through plasma membranes of porcine kidney epithelial cell line LLC-PK12007

    • Author(s)
      T.Tsutsumi et al.
    • Journal Title

      Prostagalandins and Other Lipid Mediators 83・1

      Pages: 33-41

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels of bioactive lysophospholipase D activity2007

    • Author(s)
      A.Tokumura et al.
    • Journal Title

      Life Sciences 80・18

      Pages: 1641-1649

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Production of bioactive lysophosphatidic acid by lysophospholipase D in hen egg white2007

    • Author(s)
      J.Morishige et al.
    • Journal Title

      Biochimica et Biopysica Acta 1771・4

      Pages: 491-498

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Movement of monoglyceride derived from hydrolysis of fluororescence- labeled lyso platelet-activating factor by lysophospholipase C through plasma membranes of porcine kidney epithelial cell line LLC-PK12007

    • Author(s)
      T.Tsutsumi et al.
    • Journal Title

      Prostaglandins and Other Lipid Mediators 83-1

      Pages: 33-41

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels of bioactive lysophospholipase D activity2007

    • Author(s)
      A.Tokumura et al.
    • Journal Title

      Life Sciences. 1641-1649

      Pages: 80-18

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Production of bioactive lysophosphatidic acid by lysophospholipase D in hen egg white2007

    • Author(s)
      J.Morishige et al.
    • Journal Title

      Biochimca et Biophysica Acta 1771-4

      Pages: 491-497

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Measurement of phosphatidylcholine hydroperoxides in solution and in intact membranes by the ferric-xylenol orange assay2006

    • Author(s)
      K.Fukuzawa et al.
    • Journal Title

      Analytical Biochemistry 35・91

      Pages: 18-25

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 細胞外でリゾ脂質メディエーターを産世するホスホジエステラーゼ2006

    • Author(s)
      徳村 彰
    • Journal Title

      生化学 78・12

      Pages: 1141-1154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Measurement of phosphatidylcholine hydroperoxides in solution and in intact membranes by the ferric-xylenol orange assay2006

    • Author(s)
      K.Fukuzawa et al.
    • Journal Title

      Analytical Biochemistry. 359-1

      Pages: 18-25

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phosphodiesterases that extracellularly produce lysolipid mediators2006

    • Author(s)
      A.Tokumura
    • Journal Title

      Seikagaku 78-12

      Pages: 1141-1154

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

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Published: 2008-05-27  

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