CONCENTRATION-ACTIVITY PROFILE OF THE MODULATION OF CYCLOOXYGENASE PRODUCT FORMATION BY REDUCED GLUTATHIONE IN MICROSOMAL FRACTIONS FROM THE GOAT LUNG

被引：8

作者：

BELLAN, JA

MINKES, RK

KERSTEIN, MD

SHAH, SV

KADOWITZ, PJ

CASSIN, S

MCNAMARA, DB

机构：

[1] TULANE UNIV,SCH MED,DEPT PHARMACOL,1430 TULANE AVE,NEW ORLEANS,LA 70112

[2] UNIV FLORIDA,COLL MED,DEPT PHYSIOL,GAINESVILLE,FL 32611

[3] TULANE UNIV,SCH MED,DEPT SURG,NEW ORLEANS,LA 70112

[4] TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70112

来源：

BIOCHIMICA ET BIOPHYSICA ACTA | 1990年 / 1044卷 / 03期

关键词：

(Fetal lung); GSH-dependent PGH[!sub]2[!/sub] to PGE[!sub]2[!/sub] isomerase; Prostacyclin; Prostaglandin E[!sub]2[!/sub; Reduced glutathione; Thromboxane;

D O I：

10.1016/0005-2760(90)90075-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGII2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats. GSH-dependent PGH2 to PGE2 isomerase activity in microsomal fractions from the perinatal (fetal and neonatal) goat lung was not saturable with respect to GSH and can respond to changes in GSH concentration over the range of 0.01 to 30 mM, which encompasses the full range the intracellular GSH levels reported in the literature. However, in fractions from the adult, a lower rate of PGE2 formation is observed at higher GSH concentrations. In addition, the tissue levels of GSH exhibited developmental stage-related differences with fetal being higher than neonatal or adult. The present observations may have physiologic relevance, in that decreases in pulmonary GSH levels after birth may contribute to decreases in plasma PGE2 levels by decreasing pulmonary PGE2 synthesis, thereby contributing to closure of the ductus arteriosus; conversely, increased GSH levels associated with hyperoxia may contribute to persistence of ductal patency. Formation of 6-keto-PGF1α and of TXB2 (the stable metabolites of prostacyclin and TXA2) was decreased when PGE2 formation was increased by GSH activation of PGE2 isomerase in fractions isolated from all three developmental stages. A similar pattern of product formation was observed when AA was employed as substrate. These data suggest the possibility that changes in GSH concentration may modulate eicosanoid formation in cells that contain GSH-dependent PGE2 isomerase, as well as either or both prostacyclin or thromboxane synthase(s). © 1990.

引用

页码：315 / 322

页数：8

共 43 条

[1] METABOLISM OF PROSTAGLANDIN ENDOPEROXIDE BY MICROSOMES FROM HUMAN-LUNG PARENCHYMA AND COMPARISON WITH METABOLITES PRODUCED BY PIG, BOVINE, RAT, MOUSE AND GUINEA-PIG [J].