Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size.
We compared the effect of lipid composition and particle size of triglyceride-rich low density lipoprotein (LDL) upon apoprotein B conformation and binding to the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL made triglyceride-rich by in vitro incubation with triglyceride emulsion and the neutral lipid transfer protein (R-LDL); and (c) LDL from normolipidemic individuals made acutely hypertriglyceridemic by intravenous infusion of 10% Intralipid (IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had normal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased binding to the LDL receptor on human skin fibroblasts in studies at 4 degrees C and reduced degradation at 37 degrees C. Apoprotein B conformation was assessed by circular dichroism and by analyzing the immunoreactivity of different monoclonal antibodies. HTG-LDL but not R-LDL or IV-LDL showed a change in the CD spectra and a consistent decrease in the immunoreactivity of monoclonal antibody 3F5 (2.5-fold) which recognizes an epitope adjacent to the receptor binding domain of apoprotein B. These findings suggest that in triglyceride-rich LDL, the relative content of neutral lipid in the core of LDL in the absence of changes in the size of the particle does not significantly affect apoprotein B conformation or its affinity for the LDL receptor.
Galeano
N F
NF
Department of Pediatrics, Columbia University, New York, New York 10032.
Milne
R
R
Marcel
Y L
YL
Walsh
M T
MT
Levy
E
E
Ngu'yen
T D
TD
Gleeson
A
A
Arad
Y
Y
Witte
L
L
Al-Haideri
M
M
Rumsey
S C
SC
Deckelbaum
R J
RJ
D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002942:Circular Dichroism; D006801:Humans; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010316:Particle Size; D011487:Protein Conformation; D011973:Receptors, LDL / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides