Apolipoprotein C-I modulates the interaction of apolipoprotein E with beta-migrating very low density lipoproteins (beta-VLDL) and inhibits binding of beta-VLDL to low density lipoprotein receptor-related protein.
The binding of native rabbit beta-very low density lipoproteins (beta-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of beta-VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit beta-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the beta-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the beta-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the beta-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP.
Weisgraber
K H
KH
Gladstone Foundation Laboratories for Cardiovascular Disease, Department of Pathology, University of California, San Francisco 94140-0608.
Mahley
R W
RW
Kowal
R C
RC
Herz
J
J
Goldstein
J L
JL
Brown
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D053302:Apolipoprotein C-I; D001056:Apolipoproteins C / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D002788:Cholesterol Esters / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000494:pharmacology; D011817:Rabbits; D011973:Receptors, LDL / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
D053302:Apolipoprotein C-I; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; C014409:cholesteryl oleate; D009439:Neuraminidase