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The elucidation of the mechanism of abortion/ premature birth by the key enzymes (PLA2 and COX) in the arachidonic acid cascade

Research Project

Project/Area Number 13671712
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

KOYAMA Masayasu  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00183351)

Co-Investigator(Kenkyū-buntansha) ISAKA Shigeyuki  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50346201)
TAKEMURA Masahiko  Osaka University Graduate School of Medicine, Assistant Professor, 医学部附属病院, 助手 (50294062)
SHIMOYA Koichiro  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40291950)
OTA Yukinobu  Osaka University Graduate School of Medicine, Medical Staff, 医学部附属病院, 医員(臨床研究)
東 千尋  大阪大学, 医学部・附属病院, 助教授 (20151061)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsoxytocin receptor / preterm labor / methylated DNA / uterine contraction / chorioamnionitis / transcription / prostaglandin / HNE(4-hysroxy-2-nonenal)
Research Abstract

I have focused attention to phospholipase A2 (PLA2) which has been thought to be the key enzyme associated uterine contractions and an inflammatory reaction. I developed high sensitive an enzyme activity measurement system with high-speed chromatography and measured the activity of PLA2 in serum, amniotic fluid and amniotic membrane of a clinical premature labor patient. In addition, I measured the concentration of immunoreactive PLA2 with RIA method by a specific monoclonal antibody of this enzyme (gift from Shionogi Pharmaceutical). As a result, a large quantity of PLA2 was secreted in serum and amniotic fluid of a premature labor patient and group II PLA2 principally was proved to be secreted from amniotic cells of a premature labor patient in large quantities. The concentration of the immunoreactive group II PLA2 in serum and amnion related to the enzymatic activity and the system of measurement was able to be established. Since this measurement system proved very high **ensitivity … More with HPLC, this enzyme activity measurement corollary was more superior than other inflammatory protein as a biosensor of premature labor. Furthermore, I identified manifestation of PLA2 to a premature labor patient without clinical inflammation. This result suggests that inflammation resemblance or abnormality of enzyme groups of the arachidonic acid cascade participates in onset mechanism of premature labor.
It is necessary to consider influence of the oxidation stress which guides arachidonic acid metabolism (phospholipase and cyclooxygenase) when thinking about placental infection and mechanism of premature labor. HNE (4-hydroxy-2-nonenal) is a representative lipid peroxide degradation product. Alkyl modified protein with HNE is easy to be accumulated in the tissue because of its difficulty of digestion and it might be a good marker of oxidative stress. I demonstrated that HNE is strongly expressed in the placenta with clinical inflammatory diseases and manifestation of Cox-2 mRNA in the chorionic villi was observed in addition with HNE by RY-PCR. I also demonstrated that prostaglandine E2 was clearly elevated in the culture media of chorionic tissue by the addition of HNE. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Shimoya, K., Hashimoto, K., Shimizu, T.et al.: "Cervical fluid oncofetal firbronectin as a predictor of early ectopic pregnancy Is it affected by blood contamination?"J Reprod Med. 47(8). 640-644 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, H., Kimura, T., Nakajima, A., et al.: "Detection of oxidative stress in seminal plasma and fractionated sperm from subfertile male patients"Eur J Obstet Gyn R B. 105. 155-160 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ota, Y., Shimoya, K., Zhang, Q.et al.: "The expression of secretory leukocyte protease inhibitor(SLPI) in the fallopian tube : SLPI protects the acrosome reaction of sperm from inhibitory effects of elastase"Hum Reprod. 17(10). 2517-2522 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang, Q., Shimoya, K., Ohta, Y.et al.: "Detection of fractalkine in human seminal plasma and its role in infertile patients"Hum Reprod. 17(6). 1560-1564 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Shimoya., et al.: "Cervical Fluid Oncofetal Firbronectin as a Predictor of Early Ectopic Pregnancy Is It Affected by Blood Contamination"J Reprod Med. 47(8). 640-644 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Nakamura. T.Kimura., et al.: "Detection of oxidative stress in seminal plasma and fractionated sperm from ubfertile male patients"Eur J Obstet Gyn RB. 105. 155-160 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Ota, K.Shimoya., et al.: "The expression of secretory leukocyte protease inhibitor (SLPI) in the Fallopian tube: SLPI protects the acrosome reaction of sperm from inhibitory effects of elastase"Hum Reprod. 17(10). 2517-2522 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Q.Zhang, K.Shimoya, et al.: "Detection of fractalkine in huanm seminal plasma and its role in infertile patients"Hum Reprod. 17(16). 1560-1564 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoya, K., Hashimoto, K., shimizu, T., et al.: "Cervical fetal fibronectin (fFN) as a predictor of abnormal early pregnancy-Is that affected by blood contamination?"J Reprod Med. 9(2). 97-101 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura, H., Kimura, T., Nakajima, A., et al.: "Detection of oxidative stress in seminal plasma and fractionated sperm from subfertile male patients"Eur J Obstet Gyn R B. 105. 155-160 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ota, Y., Shimoya, K., Zhang, Q., et al.: "The expression of secretory leukocyte protease inhibitor(SLPI) in the fallopian tube : SLPI protects the acrosome reaction of sperm from inhibitory effects of elastase"Hum Reprod. 17(10). 2517-2522 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang, Q., Shimoya, K., Ohta, Y., et al.: "Detection of fractalkine in human seminal plasma and its role in infertile patients"Hum Reprod. 17(6). 1560-1564 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang, Q., Shimoya, K., et al.: "production of secretory leukocyte protease inhibitor by human amniotic membrances and regulation of its concentration in amniotic fluid"Mol Hum reprod. 7(6). 573-579 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kusui, C., Kimura, T., Koyama, M., et al.: "DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression"BBRC. 289. 681-686 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] X, Zou.T, Tsutsui et al.: "The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis single-regulating kinase 1"Mol Cell Biol. 21. 4818-4828 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K, Hashimoto.T, Shimizu, K, Shimiya et al.: "Fetal cerebellum : US appearance with advancing gestational age"Radiology. 221. 70-74 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimoya, K., et al.: "Cervical fetal fibronectin(fFN)as a predictor of abnormal early pregnancy-Is that affected by blood contamination?"J Reprod Med. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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