The Regulation of Prostaglandin Synthesis at the Molecular Level of Cyclooxygenase

杰克逊9307206冯·欧拉于1932年成功分离前列腺素(PG)。在这些实验中，人们发现了该化合物的许多生物学效应中的第一个：子宫平滑肌的收缩。自从这些早期的研究以来，PG已经被认为是一种在所有哺乳动物细胞系统中合成的特异的、高活性的、短暂的局部激素。局部激素参与脂肪代谢、胰岛素释放、心脏功能调节、体温和神经系统控制以及组织炎症反应。本研究计划的总体目标是确定环氧合酶(COX)调节的分子机制。环氧合酶通过催化花生四烯酸和其他20种碳多不饱和脂肪酸的转化，在PG的生物合成中发挥核心作用。此外，还将研究因子IL-1和转化生长因子-β对环氧酶水平的特殊影响以及与PG合成相关的周转。IL-1和TGF-β是调节COX基因转录调控的细胞因子。目前的研究将使用人胚胎肺成纤维细胞和牛肺动脉内皮细胞。研究结果将为PG合成的调控机制提供重要信息。这是一项研究项目，旨在研究哺乳动物系统中控制前列腺素形成的复杂机制。前列腺素是所谓的局部激素，由于躯体应激，如温度变化、疲劳或创伤，局部组织细胞迅速产生前列腺素。为了开始了解人体如何产生荷尔蒙并控制荷尔蒙的水平，我们需要了解在荷尔蒙产生过程中起作用的关键酶的作用。这种控制系统似乎非常复杂，涉及到控制阅读信使RNA(MRNA)的特殊组件的作用。信使核糖核酸含有细胞形成前列腺素产生酶所需的信息。这项研究将有助于我们理解哺乳动物身体是如何控制体温和抵抗疲劳的，脂肪是如何形成和使用的，以及组织是如何发炎和刺激的。***

Jackson 9307206 The isolation of prostaglandin(PG) was achieved by von Euler in 1932. In these experiments the first of many biological effects of the compound was discovered; the contraction of uterine smooth muscle. Since these early studies, PG has become recognized as a specific, highly active, short-lived local hormone synthesized in all mammalian cell systems. The local hormone is involved in lipid metabolism, insulin release, the regulation of cardiac function, body temperature and nervous system control, and the tissue inflammatory response. The overall objective of this research program is to determine the molecular mechanisms which operate in the regulation of cyclooxygenase (COX). The COX enzymes play central roles in PG biosynthesis by catalyzing the conversion of arachidonic acid and certain other 20 carbon polyunsaturated fatty acids. Additionally the role of factors IL-1 and TGF-Beta will be examined for their special effect on COX enzyme levels and turnover relative to PG synthesis. IL-1 and TGF-Beta are cytokines which appear to regulate transcriptional regulation of the COX genes. The present study will use human embryo lung fibroblasts and bovine pulmonary artery endothelial cells. Results will provide important information about regulatory mechanisms which govern PG synthesis. %%% This is a research project to study the complex mechanism which operates in mammalian systems to control prostaglandin formation. Prostaglandins are so called local hormones that are produced quickly in local tissue cells as a result of corporal stress, such as temperature changes, fatigue, or wounding. To begin to understand how the body produces the hormone and controls its level, we need to learn about the action of key enzymes that operate in its production. This control systems seems to be very complicated and involves the action of special components that operate to control reading messenger RNA(mRNA). mRNA contains the information the cells need t o form the enzyme for prostaglandin production. This research will help in our understanding about how the mammalian body controls its temperature and combats fatigue, how fat is formed and used, and how tissue becomes inflamed and irritated. ***