Regulation of Prostaglandin E Synthases in Parturition

分娩中前列腺素 E 合成酶的调节

• 批准号: 6551656
• 负责人: WILLIAM E ACKERMAN
• 金额: $ 4.62万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6551656
• 关键词: birth; cell line; clinical research; cytokine; human subject; immunocytochemistry; immunoprecipitation; inflammation; isomerase; messenger RNA; muscle contraction; myometrium; northern blottings; prostaglandin E; prostaglandin endoperoxide synthase; protein protein interaction; tissue /cell culture; western blottings

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.

描述（由申请人提供）：宫内前列腺素（PG）在足月和早产的分娩过程中充当近端介质。妊娠组织内宫缩 PG（特别是 PGE2）的产生主要通过涉及诱导酶环加氧酶 2 (COX-2) 转录上调的途径发生。直到最近，COX-2 反应产物 PGH2 中末端前列腺素的生成还被认为是快速发生的，并且不受特定控制。随着最近对两种具有 PGH 至 POE 异构酶活性的酶的表征，这种观点发生了变化。人们发现，这些酶，微粒体前列腺素 E 合酶 (PGES) 和胞质 PGES，在炎症条件下对 PGE2 生成的贡献不均。在本提案中，我们打算描述这两种 PGES 同工型与 COX-2 相关的表达模式。这将使用人羊膜来源的 WISH 细胞和人羊膜原代培养物在模拟炎症条件下完成。我们建议结合免疫细胞化学，在信使 RNA 水平以及蛋白质水平（全细胞裂解物和亚细胞部分）表征微粒体和胞质 PGES 的表达模式。我们希望支持这样的假设：与其他系统一样，微粒体 PGES 在子宫收缩 POE2 的生成过程中与 COX-2 功能相关。