CHARACTERIZATION OF THE LUNG PGDH

依赖NAD+的前列腺素脱氢酶 催化前列腺素15-羟基的氧化 E系列和F系列。这一反应代表了 使这些活性化合物失活。15-羟基 不具有环戊烷环的化合物 前列腺素也被这种酶代谢。15- 观察到羟基二十碳四烯酸(15-HETE)是一种 肺组织PGDH的底物。丙二醛脱氢酶从 怀孕兔的肺组织，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 白血球12-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 调节它的活动。其他欧米伽6羟基的代谢- 含有17碳和18碳原子的脂肪酸也将 学习。将进行隔离肺灌注研究，以 确定15-HETE的代谢是否可能在整个体内发生 阿龙。诱导肺组织前列腺素脱氢酶的活性为20- 是怀孕期间的40倍，但我们的研究表明 免疫反应蛋白的数量不会增加。一个 从小鼠肺组织中分离出肺组织抑制因子。 怀孕的兔子。缓蚀剂随中性脂迁移 而且有证据表明，它由游离脂肪酸组成。 将进一步审查这一因素，以确定其身份和 以确定妊娠期间前列腺素脱氢酶活性的增加是否 由于这种抑制物的变化。这种抑制物的存在是 对理解基因的表达和调控很重要 前列腺素脱氢酶活性。一种针对PGDH的抗体已经制造出来，并将 通过免疫细胞化学对酶进行定位 在肺的光学和电子显微镜水平上的程序 和其他兔子组织。抗肺灵芝脱氢酶还将用于 鉴定并比较其免疫化学性质 从各种组织中提取的PGDH酶。前列腺素脱氢酶活性受到抑制 香烟烟雾中的物质和这种酶的损失 活动可能导致血管和呼吸道的改变。 在吸烟者中观察到。丙烯醛的作用，一种反应性的 香烟烟雾中的乙醛，将研究对PGDH活性的影响。 这项提案中描述的研究将导致更大的 该酶的性质及其功能 前列腺素和其他二十烷类化合物在肺组织中的作用 功能、妊娠、肺和心血管疾病 疾病。

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.