Oxidative modification of apolipoprotein E in human very-low-density lipoprotein and its inhibition by glycosaminoglycans

The mechanism of metal ion-catalyzed oxidative modification of apolipoprote in E (apoE) in human very-low-density lipoprotein (VLDL) and its inhibition by glycosaminoglycan (GAG) was investigated in vitro, The VLDL oxidation c atalyzed by Cu2+ led to the lipid peroxidation, the formation of aggregates , and covalent modification of apoE, The modified apoE lost heparin-binding activity. These results suggest that the lipid peroxidation of VLDL and mo dification of apoE cause impairment of lipid uptake by cells and deposit th e oxidized lipids in the tissues. The lipid peroxidation and oxidative modi fication of apoE in VLDL mediated by Cu2+ and an aqueous radical generator were suppressed by GAG, heparan sulfate, heparin, and chondroitin sulfate A , even though GAGs demonstrated no ability to scavenge alpha,alpha-diphenyl -beta-picrylhydrazyl radical. There were no relationships between inhibitor y activity of GAGs in the VLDL oxidation and their number of sulfate groups which possess chelating activity of metal ion. Therefore, it can be consid ered that the inhibition of VLDL oxidation by GAGs is possibly due to the i nteraction between GAG and VLDL which bring about the steric hindrance, int erference with the reaction between VLDL particle and the reactive oxygen s pecies. These studies suggest that GAGs preserve the biological functions o f apoE from oxidative stress. (C) 1999 Academic Press.