ARACHIDONIC ACID AND PLATELET ACTIVATING FACTOR DURING BIRTH

这个项目的长期目标是进一步了解 母体与胎儿之间的生化相互作用 对血小板活化因子和花生四烯酸代谢的释放 以及这些耳甲类动物与精神分裂症的发生和维持的关系。 分娩。将致力于阐明PAF的分解代谢 以及它与乙醇胺血浆原作为代谢产物的关系。 参与这一代谢转换的酶的活性将是 由人羊膜来源的细胞系(WISH)确定。研究将会 以确定细胞的起源和调控 血浆PAF-乙酰水解酶(PAF-AH)_2是引起PAF的酶 失活。多种类固醇激素在调节血管紧张素转换酶活性中的作用 我们将对血浆PAF-AH进行研究。从几个来源获得的巨噬细胞 来源(肺、蜕膜)由分化而成的两种形式确立 将使用HL-60和U937细胞株来研究这种机制 在调节PAF-AH方面起作用，因为这些细胞已知 将酶分泌到培养基中。雌激素的作用， 糖皮质激素和孕激素在调节PAF- 参与PAF生物合成的乙酰转移酶也将 分析过了。血浆型PAF-AH的纯化和调节 它通过类固醇激素的遗传表达将被表征。vbl.使用 在分子生物学技术中，这种酶的mRNA将是 分离并用于制备特定的探针；这些探针 将被用来确定类固醇在 PAF-AH的表达。将对这种酶进行类似的研究 溶解PAF：乙酰-辅酶A乙酰转移酶。纤溶酶原激活剂在某些疾病中的作用 将进一步调查怀孕并发症，重点是 这种强效降压药在患有高血压的女性中可能起到的作用 妊娠高血压综合征/先兆子痫。分子物种和 PAF在人羊水各室中的浓度 将被描述为。拟议的调查应提供 有关启动和维护的重要信息 分娩和PAF的参与，特别是在 胎儿和母体之间的关系。的作用 荷尔蒙环境中参与调节的关键酶 调节PAF的稳态浓度将为 孔雀在妊娠和分娩中的功能。

The long term goal of this project is to obtain a further understanding of the biochemical interactions between the mother and the fetus with regards to platelet-activating factor (PAF) and arachidonic acid metabolism release and the relationships of these autacoids with initiation and maintenance of parturition. Efforts will be directed to elucidate the catabolism of PAF and its relationship to ethanolamine plasmalogens as metabolic products. The activity of the enzymes involve in this metabolic conversion will be determined in a cell line derived from human amnion (WISH). Studies will be carried out i order to determine the cellular origin and regulation of the plasma PAF-acetylhydrolase (PAF-AH)_, the enzyme responsible for PAF inactivation. The role of various steroid hormones in the regulation of the plasma PAF-AH will be investigated. Macrophages obtained from several sources (lung, decidua) and from the differentiated form of two established cell lines (HL-60 and U937) will be employed to investigate the mechanisms operative in the regulation of PAF-AH, since these cells are known to secrete the enzyme into the culture medium. The effects of estrogens, glucocorticoids, and progestins in the regulation of the PAF- acetyltransferases that are involved in PAF biosynthesis will also be analyzed. The plasma type PAF-AH will be purified and the regulation of its genetic expression by steroid hormones will be characterized. Using the techniques of molecular biology, the MRNA for this enzyme will be isolated and employed for the preparation of specific probes; these probes will then be used for determining the effects of the steroids in the expression of PAF-AH. Similar studies will be carried out for the enzyme lysoPAF:acetyl-CoA acetyltransferase. The role of PAF in certain complications of pregnancy will be further investigated, with emphasis on the function this potent hypotensive agent may play in women with pregnancy-induced hypertension/preeclampsia. The molecular species and concentration of PAF in the various compartments of human amniotic fluid will be characterized. The investigations proposed should provide important information related to the initiation and maintenance of parturition and the participation of PAF, particularly in terms of the relationships between the fetus and the maternal compartment. The role of the hormonal environment in the regulation of the key enzymes involved in regulating the steady-state concentration of PAF will provide insights into the function of this autacoid in gestation and parturition.