Enhanced clearance from plasma of low density lipoproteins containing a truncated apolipoprotein, apoB-89.
Previously we have reported on a kindred with hypobetalipoproteinemia in which three sisters were found to be compound heterozygotes for two newly described truncated forms of apoB. apoB-40 and apoB-89. ApoB-89-containing low density lipoproteins (LDL) bound with increased affinity to cultured normal human fibroblasts and were internalized and degraded at increased rates, suggesting that the low plasma concentrations of apoB-89-LDL of the patients could be due to enhanced rates of clearance through LDL-receptors. To examine this hypothesis, apoB-89-LDL was isolated from the three study subjects and apoB-100-LDL from two control subjects. LDL was conjugated to the radioiodinated residualizing label, dilactitol tyramine (*I-DLT, containing either 125I or 131I). *I-DLT-apoB-89-LDL and *I-DLT-apoB-100-LDL were simultaneously injected into ear veins of rabbits. The clearance from plasma and hepatic accumulations of both radiolabeled LDL fractions were followed over 24 h. Fractional catabolic rates (FCR) of apoB-89-LDL were 0.105 +/- 0.012 h-1 compared to 0.054 +/- 0.007 h-1 for apoB-100-LDL. In agreement with the enhanced clearance from plasma, 1.72 to 1.87 times more *I-DLT-apoB-89-LDL than *I-DLT-apoB-100-LDL accumulated in the livers 24 h after injection. There was no significant difference in splenic accumulation, suggesting that LDL-receptors rather than scavenger receptors mediated the enhanced clearance of apoB-89-LDL. To assess further the importance of LDL-receptors, *I-DLT-apoB-89-LDL and *I-DLT-apoB-100-LDL were reductively methylated to inhibit their interactions with LDL-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Parhofer
K G
KG
Division of Atherosclerosis and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110.
Daugherty
A
A
Kinoshita
M
M
Schonfeld
G
G
D000818:Animals; D001055:Apolipoproteins B / Q000097:blood* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008745:Methylation; D011817:Rabbits; D014461:Ultracentrifugation
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; C068393:apolipoprotein B-89