Inter-molecular cross-linking of apolipoprotein E 3 with 4-hydroxy-2-nonenal in human VLDL oxidized by ferrous ioncatalyzed oxidation system and its modulation by heparin.

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Very low density lipoprotein (VLDL) freshly prepared from human plasma was oxidized and formed precipitates by ferrous ion-catalyzed oxidation system. Apolipoprotein E isoform 3 (apoE 3) in the oxidized VLDL formed aggregates and lost its heparin-binding activity with lipid peroxidation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting with antibodies against apoE 3 and 4-hydroxy-2-nonenal (HNE), and amino acid analysis of the aggregated apoE 3 indicated that apoE 3 formed inter-molecular cross-linking with HNE, which might react with ε-amino groups of lysyl residues. Heparin strongly inhibited the aggregation of apoE 3 to restore its heparin-binding activity. These findings suggest that the aggregation of apoE causes the accumulation of lipid peroxides in the precipitates of VLDL by the loss of heparin-binding activity. This may be a mechanism of the deposition of HNE-adducts in the vascular system and the brain of Alzheimer's disease. Furthermore, heparin may regulate lipid metabolism as an inhibitor of oxidative modification of VLDL.
日本電気泳動学会の論文