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Journal of Lipid Research, Vol. 18, 438-450, July 1977
Copyright © 1977 by Lipid Research, Inc.

Binding, internalization, and degradation of high density lipoprotein by cultured normal human fibroblasts

N. E. Miller , D. B. Weinstein , and D. Steinberg

Division of Metabolic Disease, Department of Medicine, University of California, San Diego, La Jolla, CA 92093

Comparative studies were made of the metabolism of plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) by cultured normal human fibroblasts. On a molar basis, the surface binding of ¹²⁵I-HDL was only slightly less than that of ¹²⁵I-LDL, whereas the rates of internalization and degradation of ¹²⁵I-HDL were very low relative to those of ¹²⁵I-LDL. The relationships of internalization and degradation to binding suggested the presence of a saturable uptake mechanism for LDL functionally related to high-affinity binding. This was confirmed by the finding that the total uptake of ¹²⁵I-LDL (internalized plus degraded) at 5 µg LDL protein/ml was 100-fold greater than that attributable to fluid or bulk pinocytosis, quantified with [¹⁴C]sucrose, and 10-fold greater than that attributable to the sum of fluid endocytosis and adsorptive endocytosis. In contrast, ¹²⁵I-HDL uptake could be almost completely accounted for by the uptake of medium during pinocytosis and by invagination of surface membrane (bearing bound lipoprotein) during pinocytosis. These findings imply that, at most, only a small fraction of bound HDL binds to the high-affinity LDL receptor and/or that HDL binding there is internalized very slowly. The rate of ¹²⁵I-HDL degradation by cultured fibroblasts (per unit cell mass) exceeded an estimate of the turnover rate of HDL in vivo, suggesting that peripheral tissues may contribute to HDL catabolism. In accordance with their differing rates of uptake and cholesterol content, LDL increased the cholesterol content of fibroblasts and selectively inhibited sterol biosynthesis, whereas HDL had neither effect.

Supplementary key words low density lipoprotein • cholesterol metabolism • pinocytosis • endocytosis

Submitted on November 4, 1976
Accepted on February 17, 1977

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