Relation of N-glycosylation of apolipoprotein B-100 to cellular metabolism of low density lipoprotein.

We studied the functional role of N-linked sugar chains of apolipoprotein (apo) B-100 of low density lipoprotein (LDL) in cholesterol metabolism. The N-linked sugar chains of apo B-100 of LDL obtained from four homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and column chromatography. They consisted of one neutral (N) and two acidic (A1, A2) fractions. The ratio of apo B-100 acidic fractions (A1+A2) varied among 4 WHHL rabbits. Serial measurements of serum cholesterol levels showed that they decreased with aging in each of 4 WHHL rabbits. We investigated the relation of the ratio of acidic sugar chains of apo B-100 to the serum cholesterol levels. Reciprocals of the serum cholesterol levels were significantly correlated with the ratio of acidic sugar chains of apo B-100 (r = 0.901, P < 0.001). To elucidate the role of N-linked sugar chains of apo B-100, we investigated cellular uptake of LDL in normal rabbit skin fibroblasts. The amounts of association, degradation and cholesteryl esterification of LDL with a lower ratio of acidic sugar chains at 37 degrees C were greater than those of LDL with a higher ratio of acidic sugar chains. These results suggest that N-glycosylation of apo B-100 may be related with serum cholesterol levels and N-linked sugar chains of apo B-100 may play an important role in cellular metabolism of LDL.