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颖且重要的模型 表征血小板的自分泌和旁分泌介质反应 激活因子。 我们的实验提供了对 PAF 受体的性质和调节特征 至少让我们看到了 PAF 作为调解者的重要性。 肝脏对全身和局部肝脏病理生理学的反应。 PAF 通过特定受体在作用中合成并明确定义 信号转导机制、糖原分解和葡萄糖的激活 输出。 在创伤反应观点中，暂时代表了一个关键 调节炎症细胞进入循环的因素 进入受损的肝脏。 在下一个资助期内，我们将追求四个 主要实验问题旨在表征：1） PAF 受体 mRNA 合成的两个关键，4) PAF 作为受体的作用 三种相关肝损伤模型中的炎症介质，例如 缺血/再灌注、胆管结扎引起的黄疸和 败血症/内毒素血症。 在每个肝损伤模型中，我们都有 测量到肝脏 PAF 含量增加，我们需要了解 这一发现的后果影响了血流动力学和 肝脏的代谢功能。 我们的努力将得到极大的帮助 在过去的资助期内开发了几种新型试剂，其中最 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节机制 将是溶解、稳定和纯化 acety1CoA::lysoPAF 乙酰转移酶很可能是关键 巨噬细胞型细胞中 PAF 合成的调节步骤。 成功的 我们提出的实验结果将产生重大影响 对我们基于知识的贡献 在哺乳动物肝脏中起作用的细胞内信号传导机制为 它对病理生理事件做出反应。