title: Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury.
abstract: Increased intracellular production of oxygen radicals is a major etiology of cell damage from many quinoid antibiotics, environmental toxicants, and hyperoxia. Enhancing the intracellular content of protective enzymes can provide a means of limiting biological damage caused by free radicals. Liposomal entrapment and intracellular delivery of superoxide dismutase to cultured porcine aortic endothelial cells increased the specific activity of cellular superoxide dismutase 6 to 12-fold. This augmented superoxide dismutase activity persisted in cultured endothelial cell monolayers and rendered these cells resistant to oxygen-induced injury. Culture of confluent endothelial cells in hyperoxia increased 51Cr and lactate dehydrogenase release in an oxygen concentration-dependent manner. Superoxide dismutase-augmented endothelial cells were resistant to oxygen damage compared to untreated controls, in a superoxide dismutase concentration-dependent manner. Free superoxide dismutase in the absence or presence of liposomes containing no enzyme had no effect on cellular enzyme activity and did not protect from oxygen damage. Liposomes made from saturated fatty acid-containing phospholipids had a small but significant protective effect on oxygen-induced cell damage. These liposomes probably increased endothelial cell membrane saturated lipid content and thereby decreased peroxidative damage when the cells were exposed to hyperoxia. Conversely, preincubation of cells with arachidonic acid increased cell arachidonic acid content, sensitivity to hyperoxia, and hyperoxia-induced production of thiobarbituric acid material. These data suggest that intracellular delivery of superoxide dismutase prevents oxygen-induced cell damage and that superoxide is an important mediator of cellular oxygen toxicity.
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology*; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008081:Liposomes; D010100:Oxygen / Q000633:toxicity*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D013552:Swine
chemical_list: D008054:Lipid Peroxides; D008081:Liposomes; D011663:Pulmonary Surfactants; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D010100:Oxygen