Effects of reactive oxygen species on prostacyclin production in perinatal rat lung cells.
A differentiation-arrested primary cell culture model was used to examine the role of reactive oxygen species in the control of prostacyclin (PGI2) production in the perinatal rat lung. Coincubation of the lung cells with arachidonic acid (AA) and xanthine (X, 0.25 mM) plus xanthine oxidase (XO, 10 mU/ml) or with AA and glucose (25 mM) plus glucose oxidase (25 mU/ml) augmented the AA-induced PGI2 output. Superoxide dismutase (10 U/ml) did not alter the X + XO effect, whereas catalase (10 U/ml) eliminated both X + XO and glucose plus glucose oxidase effects. H2O2 (1-200 microM) showed a dose-related biphasic augmentation with peak stimulation at 20 microM. Catalase again blocked this effect, but dimethylthiourea, a hydroxyl radical scavenger, did not. A 20-min pretreatment of the cells with X + XO, glucose plus glucose oxidase, or H2O2, however, diminished the capacity of the cells to convert exogenous AA to PGI2. This pretreatment effect was also blocked by catalase. The responses were similar in lung cells obtained from day 20 rat fetuses (term = 22 days) and 1-day-old newborn rats. Lactate dehydrogenase release was not detected during treatment periods but increased significantly after exposure to reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
D S
DS
Department of Paediatrics, University of Western Ontario, London, Canada.
McCallum
E A
EA
Olson
D M
DM
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D005333:Fetus; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D001095:Arachidonic Acids; D005609:Free Radicals; D014970:Xanthines; D019820:Xanthine; D015121:6-Ketoprostaglandin F1 alpha; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen