The effects of glycation/glycoxidation on the liberation of 8-epi-PGF2alpha from low density lipoprotein during its in vitro oxidation.
In individuals suffering from diabetes mellitus, low-density lipoprotein (LDL) can undergo glycoxidation, both the surface protein and the unsaturated fatty acids in the particle core experiencing oxidative damage. In these patients, plasma levels of glycated(g)/glycoxidated(go) low-density lipoprotein and of 8-epi-PGF2alpha (8-IP), a relatively stable peroxidation product 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, liberation 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 vitro results we conclude, that 1) gLDL is more prone to cell-mediated oxidation than native or goLDL and 2) the increased in vivo plasma levels of 8-IP observed in diabetes mellitus could be due to prolonged LDL-glycoxidation liberating continuously significant amounts of 8-IP.
Sobal
G
G
Department of Nuclear Medicine, University of Vienna, Austria.
Menzel
E J
EJ
Sinzinger
H
H
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D000093844:Glycated Proteins
D000975:Antioxidants; D003300:Copper; D015237:Dinoprost; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins; C075750:8-epi-prostaglandin F2alpha