CHARACTERIZATION OF THE LUNG PGDH

肺 PGDH 的特征

• 批准号: 3320859
• 负责人: Richard T. Okita
• 金额: $ 9.98万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3320859
• 关键词: acrolein; antibody; eicosanoid metabolism; eicosanoids; electron microscopy; enzyme inhibitors; enzyme mechanism; gel electrophoresis; guinea pigs; human tissue; hydroxy fatty acid; immunochemistry; laboratory rabbit; lung; placenta; pregnancy; prostaglandin E; prostaglandin F; prostaglandins

The NAD+-dependent prostaglandin dehydrogenase (PGDH) catalyzes the oxidation of the 15-hydroxyl group of prostaglandins of the E and F series. This reaction represents the major route of inactivation for these reactive compounds. 15-Hydroxy compounds that did not posses the cyclopentane ring of prostaglandins also were metabolized by this enzyme. 15- Hydroxy-eicosatetraenoic acid (15-HETE) was observed to be a substrate of the lung PGDH. The PGDH has been purified from the lung of pregnant rabbits and will be used to study the metabolism of 15-HETE and other 15-hydroxy-di- and triHETEs. 15-HETE may have important biological roles in modulating 5-and 12- lipoxygenase activities of white cells and mucus secretion in the lung, thus the metabolism of 15-HETE may be important in regulating its activity. The metabolism of other omega 6hydroxy- fatty acids that contain 17- and 18-carbon atoms also will be studied. Isolated lung perfusion studies will be performed to determine if the metabolism of 15-HETE may occur in the whole lung. The enzymatic activity of the lung PGDH is induced 20- to 40-fold during pregnancy of the rabbits but our studies indicate that the amount of immunoreactive protein does not increase. An inhibitory factor of the lung PGDH was isolated from the lungs of pregnant rabbits. The inhibitor migrated with the neutral lipid fraction and the evidence suggests it consists of free fatty acids. This factor will be examined further to determine its identity and to determine if the increase in PGDH activity during pregnancy is due to changes in this inhibitor. The presence of this inhibitor is important in understanding the expression and regulation of the PGDH activity. An antibody to the PGDH has been made and will be used to localize the enzyme by immunocytochemical procedures at the light and electron microscope levels in the lung and other rabbit tissues. The anti-lung PGDH also will be used to characterize and compare the immunochemical properties of PGDH enzymes from various tissues. PGDH activity is inhibited by substances in cigarette smoke and this loss of enzymatic activity may contribute to the vascular and airway changes observed in cigarette smokers. The effects of acrolein, a reactive aldehyde in cigarette smoke, will be studied on PGDH activity. The studies described in this proposal will lead to a greater characterization of this enzyme and the function of prostaglandins and other eicosanoid derivatives in pulmonary function, in pregnancy, and in pulmonary and cardiovascular diseases.

NAD+依赖性前列腺素脱氢酶（PGDH） 催化15-羟基的氧化 E和F系列。 该反应代表了 这些反应性化合物的失活。 15-羟基 没有取代环戊烷环的化合物 该酶也能代谢木黄酮。 15- 羟基-二十碳四烯酸（15-HETE）被观察到是一种 肺PGDH的底物。 PGDH已从 妊娠兔的肺，并将用于研究 15-HETE和其他15-羟基-二-和三-HETE的代谢。 15-HETE可能在调节5-和 12-白色细胞脂氧合酶活性和粘液分泌 肺，因此15-HETE的代谢可能是重要的 规范其活动。 其他欧米茄6羟基的代谢- 含有17和18个碳原子的脂肪酸也将被 研究了 将进行隔离肺灌注研究， 确定15-HETE的代谢是否可能发生在整个 肺。 肺PGDH的酶活性被诱导20- 25天。 40-但我们的研究表明， 免疫反应蛋白质的数量不会增加。 一个 肺PGDH的抑制因子是从肺中分离的， 怀孕的兔子 抑制剂随中性脂质迁移 部分和证据表明它由游离脂肪酸。 将进一步研究这一因素，以确定其身份， 以确定怀孕期间PGDH活性的增加是否 由于这种抑制剂的变化。 这种抑制剂的存在是 重要的是了解表达和调节的 PGDH活性。 PGDH的抗体已经制备出来，并将 用免疫细胞化学法定位酶 在肺部的光镜和电镜水平上的操作 和其他兔子组织 抗肺PGDH还将用于 表征和比较免疫化学特性 PGDH酶来自各种组织。 PGDH活性受到抑制 由于香烟烟雾中的物质和这种酶的损失， 活动可能导致血管和气道的变化 在吸烟者中观察到。 丙烯醛，一种反应性的 醛，将研究PGDH活性。 本提案中所述的研究将导致更大的 这种酶的特性和功能， 在肺内给药中的洋地黄素和其他类花生酸衍生物 功能，在怀孕期间，肺和心血管 疾病