CHARACTERIZATION OF THE LUNG PGDH

肺 PGDH 的特征

• 批准号: 3320861
• 负责人: Richard T. Okita
• 金额: $ 12.42万
• 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/3320861
• 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-羟基的前列腺素的氧化 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 不使用环戊烷环的化合物 前列腺素也通过该酶代谢。 15- 观察到羟基 - 耐盐酸苯甲酸（15- heTe）是一个 肺PGDH的底物。 PGD​​H已从 怀孕兔子的肺，将用于研究 15-Heete和其他15-羟基二甲基和Trihetes的代谢。 15-HETE在调节5和 12-白细胞和粘液分泌的脂氧合酶活性 肺，因此15-Hete的代谢可能很重要 调节其活动。 其他欧米茄6羟基的代谢 含有17碳原子和18碳原子的脂肪酸也将是 研究。 孤立的肺灌注研究将进行 确定整个15-HETE的代谢是否可能发生 肺。 肺PGDH的酶活性被诱导20- 兔子怀孕期间40倍，但我们的研究表明 免疫反应蛋白的量不会增加。 一个 从肺中分离出肺PGDH的抑制因子 怀孕的兔子。 用中性脂质迁移的抑制剂 部分和证据表明它由游离脂肪酸组成。 将进一步检查该因素，以确定其身份和 确定怀孕期间PGDH活性的增加是否为 由于该抑制剂的变化。 该抑制剂的存在是 了解理解的表达和调节 PGD​​H活动。 已经制作了对PGDH的抗体，将 用于通过免疫细胞化学定位酶 在肺中的光和电子显微镜水平上的过程 和其他兔组织。 抗肺PGDH也将用于 表征和比较 来自各种组织的PGDH酶。 PGD​​H活性被抑制 通过香烟中的物质和这种酶的损失 活动可能有助于血管变化 在吸烟者中观察到。 丙烯醛的作用，一种反应性的 将在PGDH活性上研究香烟中的醛。 该提案中描述的研究将导致更大的 该酶的表征和功能 前列腺素和肺中的其他类类衍生物 功能，怀孕以及肺和心血管 疾病。