The effects of glycation/glycoxidation on the liberation of 8-epi-PGF(2 alpha) from low density lipoprotein during its in vitro oxidation

In individuals suffering from diabetes mellitus, low-density lipoprotein (L DL) can undergo glycoxidation, both the surface protein and the unsaturated fatty acids in the particle core experiencing oxidative damage. In these p atients, plasma levels of glycated(g)/glycoxidated(go) low-density lipoprot ein and of 8-epi-PGF(2 alpha) (8-IP), a relatively stable peroxidation prod uct of arachidonic acid, are increased. This study reports on the modified oxidation of gLDL and goLDL by human umbilical vein endothelial cells or by copper cations in the absence of cells. In both systems, glycated LDL was found to be more easily oxidized than either nLDL or goLDL. In addition, li beration of 8-IP from glycoxidated LDL is significantly reduced, because a large amount of 8-IP is already formed during long-term glycation of LDL in the absence of metal chelators, i.e. during glycoxidation. From these in v itro results we conclude, that 1) gLDL is more prone to cell-mediated oxida tion than native or goLDL and 2) the increased in vivo plasma levels of 8-I P observed in diabetes mellitus could be due to prolonged LDL-glycoxidation liberating continuously significant amounts of 8-IP. (C) 2000 Harcourt Pub lishers Ltd.