LIPID METABOLISM IN STIMULATED HUMAN PLATELETS

受刺激的人体血小板中的脂质代谢

• 批准号: 3340219
• 负责人: M J BROEKMAN
• 金额: $ 4.58万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3340219
• 关键词: arachidonate; gas chromatography; hemostasis; high performance liquid chromatography; human tissue; lipid metabolism; lysophospholipids; monocyte; neutrophil; phosphatidylinositols; phospholipids; platelets; prostaglandins; thin layer chromatography; thrombosis; thromboxanes

The present proposal is aimed at an understanding of several aspects of the liberation of arachidonic acid from phospholipid stores in stimulated platelets. Since the enzyme cyclooxygenase and lipoxygenase can only utilize the free arachidonate, the mechanisms of its release, which are as yet incompletely understood, are an important control point in the formation of biologically active oxygenated products, such as the pro-aggregatory platelet-derived thromboxane A2. In addition, liberated arachidonate can be utilized by other cells to form additional, biologically active compounds such as anti-aggregatory prostacyclin by endothelial cells, and hydroxy acids and leukotrienes by leukocytes. I plan to investigate: 1) the source of arachidonate freed for cyclooxygenation from platelet phospholipids, and thereby the mechanisms by which this liberation occurs, 2) the role of albumin (a plasma protein, which avidly binds fatty acids as well as the eicosanoids thromboxane A2, prostacyclin, and leukotriene A4) in the spectrum of both released fatty acids an eicosanoids, 3) the pathway(s) by which platelets remove (lytic) lyso phospholipids formed upon stimulation, 4) whether the time course of changes in platelet content of polyphosphoinositides is consistent with the hypothesis that polyphosphoinositides might represent the site from which membrane-bound calcium is released upon platelet stimulation, and 5) the extent to which platelets might contribute arachidonic acid (and endoperoxides as well as hydro (per) oxides) to monocytes--cells which appear to have a greater capacity than PMN leukocytes to form a variety of oxygenated arachidonate products, including both thromboxane A2 and prostacyclin, as well as leukotrienes B4 and C4. The techniques to be used for most of these studies are operational in the independent laboratory of the Principal Investigator, and consist of TLC, GC and HPLC, as well as radiochemical procedures. The knowledge gained from the proposed investigations should increase our understanding of the role of platelets in the generation of bioactive eicosanoids and cell-cell interactions as related to hemostasis, thrombosis and atherosclerosis.

本提案旨在了解《公约》的几个方面， 花生四烯酸从受刺激的磷脂库中的释放 血小板 由于环氧合酶和脂氧合酶只能 利用游离花生四烯酸，其释放机制，这是作为 但尚未完全了解，是一个重要的控制点， 生物活性含氧产物的形成，例如 促聚集血小板衍生血栓素A2。 此外，解放 花生四烯酸可以被其它细胞利用以形成另外的， 生物活性化合物如抗聚集前列环素， 内皮细胞和白细胞的羟基酸和白三烯。 我 计划调查：1）花生四烯酸的来源， 血小板磷脂的环氧化，从而通过 2）白蛋白（一种血浆蛋白， 其与脂肪酸以及类花生酸类血栓烷A2强烈结合， 前列环素和白三烯A4）在这两个释放的脂肪酸谱 酸和类二十烷酸，3）血小板清除（溶解）的途径 刺激后形成的溶血磷脂，4） 血小板中聚磷酸肌醇含量的变化与 假设多磷酸肌醇可能代表了 膜结合的钙在血小板刺激时释放，和5） 血小板可能贡献花生四烯酸的程度（以及 内过氧化物以及氢（过）氧化物）到单核细胞-细胞， 似乎比中性粒细胞有更大的能力，形成各种 氧化花生四烯酸产物，包括血栓素A2和 前列环素以及白三烯B4和C4。 将使用的技术 因为这些研究中的大多数都是在独立的实验室中进行的， 主要研究者，包括TLC、GC和HPLC，以及 放射化学程序。 从建议中获得的知识 研究应该增加我们对血小板作用的理解 在生物活性类花生酸的产生和细胞-细胞相互作用中， 与止血、血栓形成和动脉粥样硬化有关。