ARACHIDONIC ACID AND PLATELET ACTIVATING FACTOR DURING BIRTH
出生期间的花生四烯酸和血小板激活因子
基本信息
- 批准号:6240848
- 负责人:
- 金额:$ 18.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-04-01 至 1998-03-31
- 项目状态:已结题
- 来源:
- 关键词:SDS polyacrylamide gel electrophoresis arachidonate birth embryo /fetus membrane enzyme activity fatty acid biosynthesis fatty acid metabolism gas chromatography mass spectrometry glucocorticoids hormone regulation /control mechanism human pregnant subject laboratory rabbit laboratory rat lipid metabolism myometrium phospholipase A2 phospholipase C phospholipids platelet activating factor progesterone protein kinase radioimmunoassay
项目摘要
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.
本项目的长期目标是进一步了解
母亲和胎儿之间的生物化学相互作用
血小板活化因子(PAF)和花生四烯酸代谢释放
以及这些自育激素与启动和维持
分娩 将致力于阐明PAF的分类
及其与作为代谢产物的乙醇胺缩醛磷脂的关系。
参与这一代谢转化的酶的活性将是
在来源于人羊膜的细胞系(WISH)中测定。 研究将
为了确定细胞起源和调节,
血浆PAF-乙酰水解酶(PAF-AH)_,负责PAF的酶
失活 各种类固醇激素在调节
将研究血浆PAF-AH。 从几种来源获得的大分子化合物
来源(肺,蜕膜)和从两个建立的分化形式
本研究以HL-60和U937细胞为研究对象,
在PAF-AH的调节中起作用,因为已知这些细胞
将酶分泌到培养基中。 雌激素的作用,
糖皮质激素和孕激素调节PAF-
参与PAF生物合成的乙酰转移酶也将被
分析了 血浆型PAF-AH将被纯化,并且调节
将表征其通过类固醇激素的遗传表达。 使用
分子生物学技术,这种酶的mRNA将是
分离并用于制备特异性探针;这些探针
然后将用于确定类固醇在
PAF-AH的表达。 将对酶进行类似的研究
lysoPAF:乙酰辅酶A乙酰转移酶。 PAF在某些疾病中的作用
将进一步调查妊娠并发症,重点是
这种有效的扩张剂可能在女性中发挥的作用
妊娠高血压/先兆子痫。 分子种类和
人羊水各隔室中PAF的浓度
将被定性。 拟议的调查应提供
与启动和维护有关的重要信息
分娩和PAF的参与,特别是在
胎儿和母体之间的关系 的作用
激素环境中的关键酶的调节参与
调节PAF的稳态浓度将提供以下见解:
这种自分泌物在妊娠和分娩中的作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN M JOHNSTON其他文献
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{{ truncateString('JOHN M JOHNSTON', 18)}}的其他基金
ARACHIDONIC ACID AND PLATELET ACTIVATING FACTOR DURING BIRTH
出生期间的花生四烯酸和血小板激活因子
- 批准号:
5212466 - 财政年份:
- 资助金额:
$ 18.32万 - 项目类别:
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