EFFECT OF OXIDATIVE STRESS ON MEMBRANE-STRUCTURE - SMALL-ANGLE X-RAY-DIFFRACTION ANALYSIS

Free radical damage to cellular membranes appears to underlie alterati ons in function in aging and various pathological processes, including cardiovascular disease. The objective of this study was to directly c haracterize changes in the molecular structure of membrane lipid bilay ers resulting from oxidative stress. Membrane samples reconstituted fr om either synthetic or cardiac phospholipids enriched with polyunsatur ated fatty acids were examined at high resolution using small-angle x- ray diffraction methods. In this study, Fe2+/ascorbate-induced lipid p eroxidation produced significant and dose-dependent alterations in the basic physical structure of the phospholipid bilayer. Electron densit y profiles (Angstrom vs. electrons/Angstrom(3)) calculated from the x- ray diffraction data showed a marked reduction in the hydrocarbon core width of dilinoleoyl phosphatidylcholine (DLPC) bilayers from 36 Angs trom to 32 Angstrom, and a decrease in overall membrane width, includi ng surface hydration, from 48.7 Angstrom to 44.6 Angstrom. In addition , a broad decrease in molecular volume was observed +/-3-10 Angstrom f rom the center of the membrane bilayer, along with interdigitation of the terminal methyl segments. Pronounced changes in the lipid bilayer structure following oxidative stress were also observed in membranes r econstituted from cardiac lipids, including a 4 Angstrom reduction in hydrocarbon core width from 40 Angstrom to 36 Angstrom and interdigita tion of the terminal methyl segments. These data provide direct eviden ce for changes in membrane hydrocarbon core width and molecular volume resulting from phospholipid peroxidation, which may contribute to per turbations in membrane structure/function relationships associated wit h aging and cardiovascular disease. (C) 1997 Elsevier Science Inc.