Interaction between oxygen and cell membranes: modification of membrane lipids to enhance pulmonary artery endothelial cell tolerance to hypoxia.
Because high partial pressures of oxygen (O2) can cause peroxidative cleavage of membrane lipids, it is plausible to hypothesize that hyperoxia alters the physical state and composition of lipids in the membranes of pulmonary endothelial cells and that manipulation of the lipid profile may modify endothelial cell tolerance to hyperoxic injury. To test this, porcine pulmonary artery endothelial cells were exposed to 95% O2 at 1 atmosphere absolute (ATA) in the presence or absence of cis vaccenic acid (CVA), a monounsaturated fatty acid (C18:1#11). Plasma membrane fluidity was assessed by fluorescence spectroscopy, plasma membrane lipid composition was quantitated using thin layer and gas chromatography, and cytotoxicity was monitored by measuring release of lactate dehydrogenase (LDH). Hyperoxia caused peroxidation of membrane lipids and decreased fluidity in three distinct lipid domains within the plasma membrane. Incubation with CVA was associated with a reduction in the degree of unsaturation of the constituent fatty acids within all plasma membrane lipid subclasses except monoglycerides. CVA-treated cells were also more resistant to hyperoxic injury as judged by LDH release. These results support the hypothesis that cells with membranes in which the fatty acyl chains are more resistant to the disordering effects of high O2 tensions may be more resistant to O2 toxicity.
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Research Service, Veterans Administration Medical Center, Gainesville, Florida 32602.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005227:Fatty Acids / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000096:biosynthesis; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D013552:Swine
D005227:Fatty Acids; D008054:Lipid Peroxides; D008563:Membrane Lipids; D010743:Phospholipids; D010100:Oxygen