title: Copper-induced peroxidation of liposomal palmitoyllinoleoylphosphatidylcholine (PLPC), effect of antioxidants and its dependence on the oxidative stress.
abstract: In an attempt to deepen our understanding of the mechanisms responsible for lipoprotein peroxidation, we have studied the kinetics of copper-induced peroxidation of the polyunsaturated fatty acid residues in model membranes (small, unilamellar liposomes) composed of palmitoyllinoleoylphosphatidylcholine (PLPC). Liposomes were prepared by sonication and exposed to CuCl(2) in the absence or presence of naturally occurring reductants (ascorbic acid (AA) and/or alpha-tocopherol (Toc)) and/or a Cu(I) chelator (bathocuproinedisulfonic acid (BC) or neocuproine (NC)). The resultant oxidation process was monitored by recording the time-dependence of the absorbance at several wavelengths. The observed results reveal that copper-induced peroxidation of PLPC is very slow even at relatively high copper concentrations, but occurs rapidly in the presence of ascorbate, even at sub-micromolar copper concentrations. When added from an ethanolic solution, tocopherol had similar pro-oxidative effects, whereas when introduced into the liposomes by co-sonication tocopherol exhibited a marked antioxidative effect. Under the latter conditions, ascorbate inhibited peroxidation of the tocopherol-containing bilayers possibly by regeneration of tocopherol. Similarly, both ascorbate and tocopherol exhibit antioxidative potency when the PLPC liposomes are exposed to the high oxidative stress imposed by chelated copper, which is more redox-active than free copper. The biological significance of these results has yet to be evaluated.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Sackler Medical School, Tel-Aviv University, 69978, Tel-Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Bittner
authors.forename: Sigal
authors.initials: S
authors.lastname: Gal
authors.forename: Ilya
authors.initials: I
authors.lastname: Pinchuk
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
authors.forename: Hadassah
authors.initials: H
authors.lastname: Shinar
authors.forename: Dov
authors.initials: D
authors.lastname: Lichtenberg
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010618:Phenanthrolines / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism*; D024505:Tocopherols / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D008081:Liposomes; D010618:Phenanthrolines; D010713:Phosphatidylcholines; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; C028559:bathocuproine sulfonate; D003300:Copper; D001205:Ascorbic Acid; D024505:Tocopherols