Journal of Lipid Research, Vol 35, 848-859, Copyright © 1994 by Lipid Research, Inc.

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Acceleration of uptake of LDL but not chylomicrons or chylomicron remnants by cells that secrete apoE and hepatic lipase

SY Choi, MC Komaromy, J Chen, LG Fong and AD Cooper
Research Institute, Palo Alto Medical Foundation, CA 94301.

ApoE is a ligand for the low density lipoprotein (LDL) receptor as well as for the LDL receptor-related protein (LRP). The enzyme hepatic lipase (HL) may also affect the uptake of lipoproteins by modifying their composition. We have tested the hypothesis that hepatic lipase and apoE can function as co-factors to alter the rate of lipoprotein uptake. Chinese hamster ovary (CHO) cells were transfected with cDNAs for rat hepatic lipase, human apoE or both HL and apoE. The secreted recombinant proteins were thoroughly characterized and had properties identical to the native proteins. Hepatic lipase and apoE were secreted at 0.17 and 1.25 micrograms/mg cell protein per hour, rates comparable to those in normal liver. 125I-labeled LDL, chylomicron remnants, or chylomicrons were added to media at concentrations near their Kd. In cells that secreted either apoE or hepatic lipase, or both apoE and hepatic lipase, LDL binding was significantly greater than with control cells (2.2-, 2-, 2-fold greater, respectively). Similar enhancement of LDL degradation was observed. In the presence of anti-LDL receptor antibodies, these values were reduced to control levels; thus, the enhanced uptake was mediated by the LDL receptor and not the LRP. The amount of LDL receptor protein, as judged by Western blotting, was similar in the various cell types. Incubation of control CHO cells with media from secreting transfected cells also increased the uptake of 125I-labeled LDL. Kinetic studies indicated that, in apoE-secreting cells, increased LDL binding is associated with a lower Kd and an unchanged Vmax as compared to the control cells; furthermore, when LDL were reisolated by column chromatography (but not by ultracentrifugation) from the incubations where apoE was being secreted, apoE was identified adherent to the LDL particles. Together, these results suggest that the effect is due to alteration of the lipoprotein and not the cell. In contrast, the uptake of 125I-labeled chylomicron remnants, and 125I-labeled chylomicrons was not greater in the transfected cells. Thus, in the amounts secreted by these cells, hepatic lipase and apoE do not convert chylomicrons to chylomicron remnants or alter the uptake of chylomicron remnants by either the LDL receptor or the LRP. The enhancement of LDL removal in cells that secrete hepatic lipase or apoE may help determine the amount of LDL removed by a particular tissue.
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