Plasma triglycerides determine low density lipoprotein composition, physical properties, and cell-specific binding in cultured cells.
The relationship between the plasma triglycerides and the LDL triglycerides of 30 normal and 48 hypertriglyceridemic subjects has been quantified; the data fit a simple adsorption isotherm, LDL triglyceride/(LDL triglyceride+LDL cholesterol ester) = 0.65 plasma triglyceride/(464 + plasma triglyceride). In vitro transfer of triglyceride from concentrated VLDL to VLDL-depleted plasma produced triglyceride-rich LDL that had similar properties. LDL uptake by HepG2 cells increased with LDL triglyceride content whereas the reverse was found with skin fibroblasts. At 37 degrees C, the cores of both normal and hypertriglyceridemic LDL were isotropic liquids. Circular dichroic spectra revealed no difference in the secondary structure of normal and triglyceride-rich LDL. The affinity of monoclonal antibody MB47, which binds to the receptor ligand of apo B-100 was independent of LDL triglyceride content. MB3, which binds near residue 1022 of apo B-100, showed a triglyceride-dependent decrease in affinity for LDL from hypertriglyceridemic subjects and from in vitro incubations. LDL with an elevated triglyceride content formed in vitro had reduced proteolytic cleavage of apo B-100 by Staphylococcus aureus V8 protease. From these data, we infer that (a) LDL triglyceride is a predictable function of plasma triglyceride, (b) triglyceride induces subtle changes in apo B-100 structure at a site that is remote from the putative receptor binding ligand, and (c) the triglyceride-dependent receptor-binding determinants of apo B-100 are recognized differently by fibroblasts and HepG2 cells.
McKeone
B J
BJ
Department of Internal Medicine, Baylor College of Medicine, Houston, Texas.
Patsch
J R
JR
Pownall
H J
HJ
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008113:Liver Neoplasms; D011973:Receptors, LDL / Q000378:metabolism*; D012016:Reference Values; D012867:Skin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*; D014407:Tumor Cells, Cultured
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; C032607:low density lipoprotein triglyceride; D002784:Cholesterol