Sublethal hydrogen peroxide inhibits alveolar type II cell surfactant phospholipid biosynthetic enzymes.
Alveolar type II cell injury by phagocytic cell-derived reactive oxygen metabolites represents a potential mechanism for the altered surfactant metabolism found in patients with the adult respiratory distress syndrome (ARDS). Previous studies demonstrated altered surfactant phospholipid metabolism after sublethal oxidant exposure. In this study, we measured intracellular ATP levels and the activities of several enzymes involved in surfactant phospholipid biosynthesis after sublethal H2O2 exposure of cultured rat alveolar type II cells. Intracellular ATP levels were reduced by 46.6% after exposure to 75 microM H2O2. The activity of CTP:phosphorylcholine cytidyltransferase was unchanged after H2O2 exposure when measured in whole cell homogenates. However, when measured in the microsomal fraction, cytidyltransferase activity significantly fell after exposure of type II cells to 75 microM H2O2. Activity in the cytosolic fractions remained unchanged. Similarly, microsomal cholinephosphotransferase was reduced after H2O2 exposure. We conclude that H2O2 decreases surfactant phosphatidylcholine biosynthesis independently of its ability to deplete intracellular ATP content. These deleterious effects may partially explain the diminished alveolar surfactant observed in patients with ARDS.
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri 63110.
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D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D006861:Hydrogen Peroxide; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase