Modification of the core lipids of low density lipoproteins produces selective alterations in the expression of apoB-100 epitopes.
The conformation of the apolipoprotein B-100 associated with low density lipoproteins (LDL) is not fixed. Rather, the conformations of several regions are subject to alteration by a variety of metabolic and therapeutic perturbations that change either the lipid compositions and/or sizes of LDL particles. However, because these perturbations simultaneously alter several structural-compositional features of the particles it has been difficult to relate structural-compositional features of LDL to apoB-100 conformations. Furthermore, in in vivo studies several days pass between samplings, thus different sets of particles are studied before and after experimental perturbation. In the present experiments more discrete perturbations of LDL were obtained in vitro by incubating LDL with very low density lipoproteins (VLDL) in the presence of partially purified human plasma lipid transfer proteins. The conformations of apoB on the LDL particles then were examined a) by probing epitope expression and b) by examining interactions between LDL and LDL-receptors in cultured human fibroblasts. During incubations with VLDL and lipid transfer proteins, the diameters of LDL particles decreased; the percentage composition of LDL triglycerides increased three-to fivefold; concomitantly, cholesteryl esters decreased. Lipid transfer protein was required for the transfer to occur and the magnitude of the increase in LDL-triglycerides depended upon the duration of incubation, the ratio of VLDL/LDL, and unknown properties specific to the various LDL preparations. The fact that the triglyceride contents of all LDL preparations were not identically affected suggests that initial packaging of the core region may affect capacity for lipid exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
M
M
Kinoshita
E S
ES
Krul
G
G
Schonfeld
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000276:immunology*; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D008077:Lipoproteins, LDL / Q000032:analysis / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D011487:Protein Conformation; D011973:Receptors, LDL / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D002352:Carrier Proteins; D000939:Epitopes; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; C030363:lipid transfer protein; C032607:low density lipoprotein triglyceride