OXIDATIVE MODIFICATION OF HUMAN LIPOPROTEINS BY LIPOXYGENASES OF DIFFERENT POSITIONAL SPECIFICITIES

Cellular lipoxygenases have been implicated in foam cell formation dur ing the early stages of atherogenesis. We studied the interaction of l ipoxygenases of different positional specificities with human lipoprot eins and found that the arachidonate 15-lipoxygenases of rabbit and hu mans and the arachidonate 12-lipoxygenase of porcine leukocytes oxygen ate lipoproteins as indicated by the formation of oxygenated lipids an d changes in electrophoretic mobility of low density lipoprotein. The arachidonate 12-lipoxygenase of human platelets, the recombinant arach idonate 5-lipoxygenase of human leukocyte, and the soybean lipoxygenas e I were less effective in oxidizing human LDL. As a major oxygenation product, esterified 13S-hydro(pero)xy-9Z,11E-octadecadienoic acid was identified for both the rabbit reticulocyte 15- and the porcine leuko cyte 12-lipoxygenase. In addition, esterified -hydro(pero)xy-5,8,11,13 (Z,Z,Z,E)-eicosatetraenoic acid (for the rabbit 15-lipoxygenase) and - hydro(pero)xy-5,8,10,14(Z,Z,E,Z)-eicosatetraenoic acid (for the porcin e 12-lipoxygenase) as well as small amounts of racemic 9-hydro(pero)xy -10,12-octadecadienoic acid isomers were detected. More than 90% of th e oxygenated polyenoic fatty acids were found in the ester lipid fract ion, particularly in the cholesteryl esters and in various phospholipi d classes (phosphatidylcholine and phosphatidylethanolamine). The poss ible biological significance of lipoxygenase-induced oxidative modific ation of lipoproteins in the pathogenesis of atherosclerosis is discus sed.