Nitrogen dioxide-induced changes in cell membrane fluidity and function.
Nitrogen dioxide (NO2), an environmental oxidant pollutant, is toxic to lung cells. One of the postulated mechanisms of NO2-induced pulmonary injury involves peroxidation of membrane lipids. Therefore, we evaluated the effect of 5 ppm NO2 exposure on membrane lipid fluidity, uptake of 5-hydroxytryptamine (5-HT), lactate dehydrogenase (LDH) release, and formation of lipid peroxides in porcine pulmonary artery and aortic endothelial cells in culture. After 3- to 24-h exposure, cells were labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH), an aromatic hydrocarbon that partitions into the hydrophobic interior of the lipid bilayer of cell membranes. Membrane fluidity was monitored by measuring changes in rotational relaxation time (rho) for DPH by fluorescence spectroscopy. Reductions in membrane fluidity increase the value of rho. The 5-HT uptake was calculated from the disappearance of 1 X 10(-6) M 14C-5-HT from the medium, and LDH release and lipid peroxide formation were measured by spectrophotometric methods. The NO2 caused a significant increase in rhoDPH in both types of endothelial cells after 3 h and progressed with further exposure to NO2. Exposure to NO2 for 24 h, but not 3 or 12 h, significantly (p less than 0.05) reduced 5-HT uptake, increased (p less than 0.01) LDH release, and increased (p less than 0.05) lipid peroxide formation in both pulmonary artery and aortic endothelial cells. These results suggest that oxidant injury caused by NO changes the physical state of membrane lipids, impairs membrane function, and contributes to the biochemical and metabolic abnormalities in the cells.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D009585:Nitrogen Dioxide / Q000633:toxicity*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013552:Swine; D013997:Time Factors
D008054:Lipid Peroxides; D012701:Serotonin; D007770:L-Lactate Dehydrogenase; D009585:Nitrogen Dioxide