Acetylated low density lipoprotein reduces its ligand activity for the scavenger receptor after interaction with reconstituted high density lipoprotein.
Complexes of apolipoprotein A-I (apoA-I) with phospholipids are known to induce cholesterol efflux from cells. In a cholesteryl ester accumulation system in which rat peritoneal macrophages were incubated with acetylated low density lipoprotein (acetyl-LDL) and either dimyristoylphosphatidylcholine complexes (DMPC/apoA-I) or native high density lipoprotein (HDL), DMPC/apoA-I exhibited a much stronger effect than native HDL in preventing cholesteryl ester accumulation. The mechanism for this phenomenon was investigated in the present study. After 18 h incubation with DMPC/apoA-I in a cell-free system, acetyl-LDL was re-isolated from DMPC/apoA-I by Sephacryl S-300 gel filtration chromatography. Re-isolated acetyl-LDL exhibited an increase in its phospholipid content by 86% as well as a reduction in the electrophoretic mobility. Its endocytic degradation by macrophages was reduced by 60% when compared with control acetyl-LDL, suggesting a significant reduction in the ligand activity for the macrophage scavenger receptor. Transfer of apolipoproteins between acetyl-LDL and DMPC/apoA-I did not occur. These results indicate that transfer of DMPC from DMPC/apoA-I to acetyl-LDL weakens the ligand activity for the scavenger receptor due probably to a decrease in net negative charge. This study demonstrated for the first time that lipid modification (change in the lipid moiety) of acetyl-LDL can induce alteration in its apolipoprotein moiety, leading to a significant loss of its biological activity. Because discoidal HDLs are known to occur in vivo, this phenomenon may explain one of the anti-atherogenic functions of HDL in vivo.
Miyazaki
A
A
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
Sakai
M
M
Suginohara
Y
Y
Hakamata
H
H
Sakamoto
Y
Y
Morikawa
W
W
Horiuchi
S
S
D000818:Animals; D016632:Apolipoprotein A-I / Q000302:isolation & purification; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D002850:Chromatography, Gel; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; C023511:cholesteryl oleyl ether; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine