The Regulation of Prostaglandin Synthesis at the Molecular Level of Cyclooxygenase

前列腺素（PG）的分离于1932年由冯·欧拉（von Euler）实现。在这些实验中，发现了这种化合物的许多生物效应中的第一个；子宫平滑肌的收缩。自这些早期研究以来，PG已被认为是一种在所有哺乳动物细胞系统中合成的特异性、高活性、短寿命的局部激素。局部激素参与脂质代谢、胰岛素释放、心功能调节、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在环加氧酶（COX）调节中起作用的分子机制。COX酶通过催化花生四烯酸和其他一些20碳多不饱和脂肪酸的转化，在PG生物合成中起着核心作用。此外，IL-1和tgf - β因子对COX酶水平和相对于PG合成的转换的特殊影响将被研究。IL-1和tgf - β是调节COX基因转录调节的细胞因子。本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。这是一个研究哺乳动物系统中控制前列腺素形成的复杂机制的研究项目。前列腺素是所谓的局部激素，是由于身体压力（如温度变化、疲劳或受伤）在局部组织细胞中迅速产生的。为了开始了解人体如何产生激素并控制其水平，我们需要了解在其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，涉及控制阅读信使RNA（mRNA）的特殊成分的作用。mRNA包含细胞生成前列腺素所需的酶的信息。这项研究将有助于我们了解哺乳动物的身体是如何控制体温和对抗疲劳的，脂肪是如何形成和使用的，以及组织是如何发炎和发炎的。* * *

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. ***