REGULATION OF LIPID AUTOCOIDS IN CARDIOVASCULAR CELLS

心血管细胞中脂质类物质的调节

• 批准号: 3346744
• 负责人: Stephen M Prescott
• 金额: $ 11.71万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346744
• 关键词: G protein; adenosinetriphosphatase; arachidonate; biological signal transduction; calcium; clone cells; dogs; eicosanoid metabolism; esters; fibroblasts; gas chromatography mass spectrometry; high performance liquid chromatography; leukotrienes; macrophage; myocardial infarction; neutrophil; pericardium; phospholipids; platelet activating factor; prostaglandin endoperoxide synthase; prostaglandins; protein kinase C; radioimmunoassay; thin layer chromatography; tissue /cell culture; vascular endothelium

The goal of this project is to understand how the production of eicosanoids (prostaglandins and leukotrienes) and platelet- activating factor are regulated in several cells relevant to cardiovascular disease. Eicosanoids are oxygenated metabolites of arachidonic acid that have diverse, potent effects on pathophysiological processes. Their production by cardiac cells (including the pericardium, ventricular fibroblasts, and endothelial cells) and by blood cells involved in cardiac injury and repair (neutrophils and monocytes/macrophages) may influence inflammation, blood flow, and electrical and mechanical properties in the diseased heart. Platelet-activating factor (PAF) is a unique phospholipid (1-0-alkyl-2-acetyl-sn-glycero-3- phosphocholine) that potently activates leukocytes and platelets, and has marked hemodynamic effects. Its production by endothelium could serve as a mechanism to target inflammatory cells to an appropriate area or, if incorrectly regulated, could result in vascular injury, thrombosis, and infarction. Both eicosanoids and PAF production are tightly regulated by cells, and the regulation has many common features. The specific aims of this project are directed at describing the cellular mechanisms by which the initial step in both pathways, phospholipase activation, is achieved and how regulation is exerted at other steps in the pathways. The cells to be studied have been chosen for their relevance to cardiovascular disease and their suitability as experimental models for the relevant biochemical processes. We will examine several mechanisms for signal transduction that have been implicated by us and others in those processes, and will extensively utilize our finding of altered regulation at different times in culture as a probe for the regulatory mechanisms. Specific issues to be examined include the roles of protein kinase C, Ca flux, and G proteins in regulating PAF and eicosanoid production. The studies will use isolated cells and cultured cells that are metabolically labeled, or used as a source for enzymatic assays, followed by analytical procedures including chromatography, immunoassay, spectrometry, and electrophoresis.

这个项目的目标是了解如何生产 二十碳二烯(前列腺素和白三烯)和血小板- 激活因子在几个与以下相关的细胞中被调节 心血管疾病。二十烷类化合物是含氧代谢产物。 花生四烯酸具有不同的，有效的影响 病理生理过程。它们由心肌细胞产生 (包括心包、心室成纤维细胞和内皮细胞 细胞)和参与心脏损伤和修复的血细胞 (中性粒细胞和单核/巨噬细胞)可能会影响 炎症、血液流动、电气和机械 疾病心脏中的财产。血小板活化因子(PAF) 是一种独特的磷脂(1-0-烷基-2-乙酰基-SN-甘油-3- 能有效激活白细胞和血小板的磷胆碱)， 并具有明显的血流动力学效果。它的生产由 内皮细胞可作为靶向炎症的机制 细胞到适当的区域，或者，如果调控不当，可能 导致血管损伤、血栓形成和脑梗塞。两者都有 二十烷基类化合物和PAF的产生受到细胞的严格调控，并且 该规定有许多共同特点。的具体目标 这个项目旨在通过以下方式描述细胞机制 这是两条通路的第一步，磷脂酶的激活， 是如何实现的，以及在 小路。将被研究的细胞已经被选择用于他们的 与心血管疾病的相关性及其适宜性 相关生化过程的实验模型。我们 将研究几种信号转导机制，这些机制具有 被我们和其他人牵连到这些过程中，并将 广泛利用我们在不同领域发现的法规变化 时代在文化中作为调控机制的探索者。 要研究的具体问题包括蛋白激酶的作用。 C、Ca通量和G蛋白在调节PAF和二十烷类化合物中的作用 制作。这些研究将使用分离的细胞和培养的细胞 代谢性标记的或用作酶的来源的 分析，然后是分析程序，包括 层析、免疫分析、光谱分析和 电泳法。