Lipid peroxidation changes the expression of specific epitopes of apolipoprotein A-I.
Incubation of human serum or high density lipoprotein (HDL) at 37 degrees C in the presence of Fe2+, Fe2+/Fe3+, or Mn2+ results in the increased immunoreactivity (up to 12-, 40-, and 80-fold, respectively) of specific apoA-I epitopes identified as 3D4 and 6B8, while Mg2+, Ca2+, or Cu2+ have minimal or nonsignificant effects. The effect of Mn2+ on the 3D4 epitope requires a specific association with lipids since it can be observed with HDL but not with apoHDL, even in the presence of other lipoproteins. The increase in immunoreactivity noted with Fe2+/Fe3+ or Mn2+ can be blocked with either EDTA or antioxidants (GSH and ascorbic acid), suggesting that it takes place during a peroxidative reaction of the lipids. The peroxidation of lipids which accompanies the increase in immunoreactivity does cross-link apoA-I both with itself and with apoA-II but does not cleave the molecule. The apoA-I-containing lipoproteins which float between 1.18 and 1.22 g/ml and have a pre B-electrophoretic migration are characterized by a very low immunoreactivity with monoclonal antibody 3D4 but are 10-fold or more responsive to Mn2+ treatment than other lipoprotein subfractions, thus demonstrating heterogeneity under oxidative conditions. Proteoliposomes containing apoA-I, cholesterol, and dilinoleyl-lecithin are sensitive to Mn2+ treatment, but not those made with dioleyl- or dimyristoyl-lecithins. However, the increase in 3D4 immunoreactivity is weak and transient and is followed by the disappearance of the epitope caused by cross-linking. We conclude that lipid peroxidation can specifically cross-link apoA-I and change its conformation and antigenicity.
Marcel
Y L
YL
Laboratory of Lipoprotein Metabolism, Clinical Research Institute, Montreal, Quebec, Canada.
Jewer
D
D
Leblond
L
L
Weech
P K
PK
Milne
R W
RW
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D015227:Lipid Peroxidation; D008075:Lipoproteins, HDL / Q000097:blood; D008081:Liposomes; D008315:Malondialdehyde / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology*; D011510:Proteolipids / Q000302:isolation & purification; D011863:Radioimmunoassay
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D000939:Epitopes; D008075:Lipoproteins, HDL; D008081:Liposomes; D011510:Proteolipids; C020485:proteoliposomes; D008345:Manganese; D008315:Malondialdehyde; D007501:Iron