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

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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