Regulation of Prostaglandin E Synthases in Parturition

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Intrauterine prostaglandins (PGs) act proximal mediators in the process of parturition, both at term and preterm. The production of uterotonic PGs (particularly PGE2) within gestational tissues occurs primarily via a pathway involving transcriptional up-regulation of the inducible enzyme, cyclooxygenase-2 (COX-2). Until recently, the generation of terminal prostanoids from the COX-2 reaction product, PGH2, was thought to occur rapidly and under no particular control. This view has changed with the recent characterization of two enzymes possessing PGH to POE isomerase activity, It has been discovered that these enzymes, microsomal prostaglandin E synthase (PGES) and cytosolic PGES, contribute unequally to the generation of PGE2 under inflammatory conditions. In this proposal, we intend to characterize the expression patterns of these two PGES isoforms in relation to COX-2. This will be done using human amnion-derived WISH cells and primary cultures of human amnion, under simulated inflammatory conditions. We propose to characterize the expression patterns of microsomal and cytosolic PGES at the messenger RNA level and at the and at the protein level (in both whole cell lysates and subcellular fractions), combined with immunocytochemistry. We hope to support the hypothesis that, as in other systems, microsomal PGES is functionally linked to COX-2 in the generation of uterotonic POE2.