AGEPC--A POTENT LIPID BIOCHEMICAL MEDIATOR IN LIVER

AGEPC--肝脏中有效的脂质生化介质

• 批准号: 2139097
• 负责人: MERLE S OLSON
• 金额: $ 26.95万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2139097
• 关键词: acyltransferase; bile ducts; blood toxicology; clone cells; cytokine receptors; eicosanoids; enzyme activity; glycogenolysis; hemodynamics; inflammation; jaundice; laboratory rat; liver ischemia /hypoxia; liver metabolism; macrophage; messenger RNA; northern blottings; nuclear runoff assay; phosphoglycerides; platelet activating factor; protein purification; protein tyrosine kinase; reperfusion; vasoconstrictors

During the past decade the accomplishments of our research effort have established the liver as a novel and important model in which to characterize the autocrine and paracrine mediator response of platelet- activating factor. Our experiments have provided insights into the nature and regulatory characteristics of the PAF receptor and have provided at least a glimpse of the importance of PAF as a mediator of hepatic responses to systemic and localized hepatic pathophysiology. PAF is synthesized in Acting through specific receptors and well defined signal transduction mechanisms, activation of glycogenolysis and glucose output. Temporally later in a trauma-response view, represents a key factor in regulating the entry of inflammatory cells from the circulation into the compromised liver. In the next grant period we will pursue four major experimental issues designed to characterize: 1) the regulation of two key of PAF receptor mRNA synthesis, and 4) the role of PAF as an inflammatory mediator in three relevant models of hepatic injury, e.g., ischemia/reperfusion, bile duct ligation-induced jaundice and sepsis/endotoxemia. In each of these hepatic injury models we have measured an increase in the hepatic PAF content and we need to understand the consequences of this finding which impinge upon the hemodynamic and metabolic functions of the liver. Our efforts will be aided greatly by several novel reagents developed during the past grant period, the most important of which are specific anti-PAF receptor antibodies to be employed in studies of the regulatory mechanisms of the proposed study will be the solubilization, stabilization and purification of the acety1CoA::lysoPAF acetyltransferase which most probably is the key regulatory step in PAF synthesis in macrophage-type cells. Successful outcomes from our proposed experiments will make a significant contribution to our knowledge-based concerning the inter- and intracellular signaling mechanisms operative in the mammalian liver as its responds to pathophysiological episodes.

在过去的十年里，我们的研究工作取得了成就， 建立了肝脏作为一种新的和重要的模型， 表征血小板的自分泌和旁分泌介体反应， 活化因子 我们的实验提供了对 PAF受体的性质和调节特性， 至少提供了一个PAF作为调解人的重要性一瞥， 肝脏对全身和局部肝脏病理生理学的反应。 PAF 是通过特定的受体合成的， 信号转导机制，糖原分解和葡萄糖的激活 输出. 从创伤反应的角度来看， 调节炎性细胞从循环进入的因子 转移到受损的肝脏 在下一个资助期内，我们将追求四个 主要的实验问题，旨在表征：1）监管 血小板激活因子受体mRNA合成的两个关键，以及4）血小板激活因子作为受体mRNA合成的作用 炎症介质在三种相关的肝损伤模型中，例如， 缺血/再灌注、胆管结扎诱导的黄疸和 败血症/内毒素血症。 在这些肝损伤模型中， 测量到了肝脏PAF含量的增加，我们需要了解 这一发现对血流动力学的影响， 肝脏的代谢功能。 我们的努力将大大有助于 在过去的赠款期间开发了几种新试剂， 其中重要的是特异性抗PAF受体抗体， 用于研究拟议研究的调节机制 将是溶解，稳定和纯化的 acety 1CoA：：lysoPAF乙酰转移酶，这很可能是关键 巨噬细胞型细胞PAF合成的调节步骤。 成功 我们所提出的实验的结果将使一个重要的 对我们知识基础的贡献， 在哺乳动物肝脏中起作用的细胞内信号传导机制， 它对病理生理事件的反应