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 apolipoprotein E (apoE) in human very-low-density lipoprotein (VLDL) and its inhibition by glycosaminoglycan (GAG) was investigated in vitro. The VLDL oxidation catalyzed 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 modification of apoE cause impairment of lipid uptake by cells and deposit the oxidized lipids in the tissues. The lipid peroxidation and oxidative modification 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 inhibitory activity of GAGs in the VLDL oxidation and their number of sulfate groups which possess chelating activity of metal ion. Therefore, it can be considered that the inhibition of VLDL oxidation by GAGs is possibly due to the interaction between GAG and VLDL which bring about the steric hindrance, interference with the reaction between VLDL particle and the reactive oxygen species. These studies suggest that GAGs preserve the biological functions of apoE from oxidative stress.
Arai
H
H
Department of Nutrition, Yamaguchi Prefectural University, 3-2-1 Sakurabatake, Yamaguchi, 753-8502, Japan.
Kashiwagi
S
S
Nagasaka
Y
Y
Uchida
K
K
Hoshii
Y
Y
Nakamura
K
K
D000328:Adult; D000447:Aldehydes / Q000032:analysis / Q000378:metabolism; D000544:Alzheimer Disease; D000578:Amidines / Q000494:pharmacology; D001057:Apolipoproteins E / Q000378:metabolism*; D015764:Bepridil / Q000031:analogs & derivatives / Q000378:metabolism; D001713:Biphenyl Compounds; D002614:Chelating Agents / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000494:pharmacology; D019327:Copper Sulfate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000187:drug effects*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D010851:Picrates; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000447:Aldehydes; D000578:Amidines; D001057:Apolipoproteins E; D001713:Biphenyl Compounds; D002614:Chelating Agents; D002788:Cholesterol Esters; D003911:Dextrans; D016166:Free Radical Scavengers; D006025:Glycosaminoglycans; D008079:Lipoproteins, VLDL; D010851:Picrates; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C081459:cholesteryl ester hydroperoxide; C046728:2,2'-azobis(2-amidinopropane); D015764:Bepridil; D006493:Heparin; D002809:Chondroitin Sulfates; C004931:1,1-diphenyl-2-picrylhydrazyl; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D019327:Copper Sulfate