Oxidative Modification of Apolipoprotein E3 and Its Modulation by Heparin Binding

Apolipoprotein E (apoE) in very low density lipoprotein (VLDL) lost its heparin binding activity and formed its aggregates with lipid peroxidation by an oxidation system consisting of ferrous sulfate in saline under aerobic conditions. SDS polyacrylamide gel electrophoresis and amino acid analysis of the aggregated apoE indicated the inter-molecular cross-linking and the oxidative modification of basic amino acid residues. The presence of 1% heparin inhibited the oxidative modification of apoE to restore its heparin binding activity. These findings suggest that the oxidative modification of apoE in VLDL causes the precipitates rich in lipid peroxides and the decrease in the rate of VLDL uptake via binding to heparin on the surface of cells. This may be a possible mechanism of the accumulation of oxidized lipids in the vascular system and of the deposit of apoE in senile plaques in Alzheimer's disease.

アポリポ蛋白E

ヘパリン

酸化修飾

アルツハイマー病

分子間架橋