AGEPC--A POTENT LIPID BIOCHEMICAL MEDIATOR IN LIVER

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 血小板自分泌和旁分泌介质反应的特征 激活因子。我们的实验提供了对 PAF受体和HAVE的性质和调节特性 提供了至少一瞥PAF作为 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，并被很好地定义 信号转导机制、糖原分解和葡萄糖的激活 输出。在创伤反应视图中，在稍后的时间内，代表着一个关键 调节炎症细胞从循环进入的因素 进入受损的肝脏。在下一个资助期内，我们将推行四项 旨在表征的主要实验问题：1)调节 PAF受体mRNA合成的两个关键；4)PAF作为一种 炎症介质在三种相关的肝损伤模型中的作用，例如， 缺血/再灌流、胆管结扎诱导的黄疸和 败血症/内毒素血症。在每一种肝损伤模型中，我们都有 测量到肝脏PAF含量的增加，我们需要了解 这一发现对血液动力学和 肝脏的代谢功能。我们的努力将得到极大的帮助 在过去的赠款期间开发了几种新的试剂，最 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控机制 将增溶、稳定和提纯 乙酰1CoA：：lysoPAF乙酰转移酶，很可能是关键 巨噬细胞中PAF合成的调节步骤。成功 我们提议的实验结果将使 对我们的知识基础的贡献，关于国际和 哺乳动物肝脏AS的细胞内信号机制 它对病理生理插曲有反应。

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.