人真蜕膜（壁蜕膜）组织中前列腺素的失活：前列腺素脱氢酶的底物特异性

Inactivation of prostaglandins in human decidua vera (parietalis) tissue: substrate specificity of prostaglandin dehydrogenase.

作者信息

Casey M L, Delgadillo M, Cox K A, Niesert S, MacDonald P C

机构信息

Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235.

出版信息

Am J Obstet Gynecol. 1989 Jan;160(1):3-7. doi: 10.1016/0002-9378(89)90076-8.

DOI:10.1016/0002-9378(89)90076-8

PMID:2912098

Abstract

Prostaglandin dehydrogenase catalyzes the initial reaction in the inactivation of prostaglandin E2 and F2 alpha. To address the potential importance of this enzyme in regulating the tissue levels of active prostaglandins, we evaluated the kinetic properties of prostaglandin dehydrogenase in uterine decidua vera tissue of women. Specifically, we characterized the enzyme activity under optimal in vitro conditions in cytosolic fractions of uterine decidua vera tissue obtained at term and compared the substrate and cosubstrate specificities of prostaglandin dehydrogenase in cytosolic fractions of decidual tissues. The incubation conditions were optimized with either prostaglandin E2 or F2 alpha and nicotinamide-adenine dinucleotide or nicotinamide-adenine dinucleotide phosphate as substrates to ensure linearity of product formation with time of incubation and protein concentration. The apparent Michaelis-Menten constant of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase for prostaglandin E2 was 5.5 mumol/L. The apparent Michaelis-Menten constant of nicotinamide-adenine dinucleotide phosphate-dependent prostaglandin dehydrogenase for prostaglandin F2 alpha was 15 mumol/L. Prostaglandin E2 serves as a better substrate for prostaglandin dehydrogenase than does prostaglandin F2 alpha, irrespective of the cosubstrate. In cytosolic fractions of decidual tissues, the specific activity (apparent Vmax) of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase was greater than that of nicotinamide-adenine dinucleotide phosphate-dependent prostaglandin dehydrogenase. In addition, we found that in decidual tissue obtained before or after the onset of labor, the specific activity of prostaglandin dehydrogenase varied widely. In tissues obtained after delivery by cesarean section, no significant differences were apparent in the specific activity of the enzyme before (9.3 to 125.8 nmol/min/mg protein) and after (27.8 to 103.4 nmol/min/mg protein) the onset of labor. In cytosolic fractions of decidual tissue obtained after vaginal delivery, the specific activity of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase ranged from undetectable levels to 38.4 nmol/min/mg protein. We speculate that nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase in decidua serves to regulate the levels of bioactive prostaglandins in decidua vera tissue and the amounts of prostaglandins (and metabolites) produced in decidua or fetal membranes that reach myometrium and fetal membranes and enter maternal blood and amniotic fluid.

摘要

前列腺素脱氢酶催化前列腺素E2和F2α失活的初始反应。为了探讨该酶在调节活性前列腺素组织水平方面的潜在重要性，我们评估了女性子宫真蜕膜组织中前列腺素脱氢酶的动力学特性。具体而言，我们在足月时获得的子宫真蜕膜组织胞质部分的最佳体外条件下对酶活性进行了表征，并比较了蜕膜组织胞质部分中前列腺素脱氢酶的底物和辅酶特异性。以前列腺素E2或F2α以及烟酰胺腺嘌呤二核苷酸或烟酰胺腺嘌呤二核苷酸磷酸作为底物优化孵育条件，以确保产物形成随孵育时间和蛋白质浓度呈线性关系。烟酰胺腺嘌呤二核苷酸依赖性前列腺素脱氢酶对前列腺素E2的表观米氏常数为5.5 μmol/L。烟酰胺腺嘌呤二核苷酸磷酸依赖性前列腺素脱氢酶对前列腺素F2α的表观米氏常数为15 μmol/L。无论辅酶如何，前列腺素E2作为前列腺素脱氢酶的底物比前列腺素F2α更好。在蜕膜组织的胞质部分中，烟酰胺腺嘌呤二核苷酸依赖性前列腺素脱氢酶的比活性（表观Vmax）大于烟酰胺腺嘌呤二核苷酸磷酸依赖性前列腺素脱氢酶的比活性。此外，我们发现，在分娩开始前或后获得的蜕膜组织中，前列腺素脱氢酶的比活性差异很大。在剖宫产分娩后获得的组织中，分娩开始前（9.3至125.8 nmol/min/mg蛋白质）和后（27.8至103.4 nmol/min/mg蛋白质）酶的比活性没有明显差异可见。在阴道分娩后获得的蜕膜组织胞质部分中，烟酰胺腺嘌呤二核苷酸依赖性前列腺素脱氢酶的比活性范围从检测不到到38.4 nmol/min/mg蛋白质。我们推测，蜕膜中烟酰胺腺嘌呤二核苷酸依赖性前列腺素脱氢酶有助于调节子宫真蜕膜组织中生物活性前列腺素的水平以及蜕膜或胎膜中产生的、到达子宫肌层和胎膜并进入母体血液和羊水的前列腺素（及其代谢物）的量。