The Low Density Lipoprotein Receptor-related Protein Contributes to Selective Uptake of High Density Lipoprotein Cholesteryl Esters by SW872 Liposarcoma Cells and Primary Human Adipocytes

Abstract

The concept that selective transfer of high density lipoprotein (HDL)-derived cholesteryl esters (CE) does not require lipoprotein internalization has been challenged recently by evidence that implicates HDL recycling during the selective uptake process. This has prompted us to examine the role of the low density lipoprotein receptor-related protein (LRP) in selective uptake. LRP is an endocytic receptor for lipoprotein lipase (LpL) and apolipoprotein E (apoE) ligands that are able to mediate selective uptake. We report that molecules that interfere with ligand binding to LRP, such as the receptor-associated protein (RAP), suramin, ␣ 2 -macroglobulin, or lactoferrin, inhibit HDL-CE selective uptake by human primary adipocytes and SW872 liposarcoma cells by 35-50%. This partial inhibition of selective uptake from total HDL was not due to preferential inhibition of the HDL 2 or HDL 3 subfractions. Selective uptake by the scavenger receptor BI was not inhibited by RAP, excluding its involvement. Furthermore, in SW872 cells in which LRP was reduced to 14% of control levels by stable antisense expression, selective uptake was attenuated by at least 33%, confirming a role for LRP in this process. RAP, ␣ 2 -macroglobulin, lactoferrin, and suramin (individually or in paired combinations) also attenuated selective uptake of HDL-CE by primary human adipocytes by about 40%. On the other hand, human skin fibroblasts express LRP abundantly but lack the capacity for selective uptake, demonstrating that other molecules are required. In SW872 cells, exogenous apoE or LpL can facilitate selective uptake but only the apoE-enhanced uptake can be inhibited by RAP, implicating apoE as a likely co-mediator. We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake.

Association of Circulating Lactoferrin Concentration and 2 Nonsynonymous LTF Gene Polymorphisms with Dyslipidemia in Men Depends on Glucose-Tolerance Status

“…Lactoferrin has previously been described to inhibit the selective uptake of HDL cholesteryl esters by 35%-50% in human primary adipocytes and SW872 liposarcoma cells (22 ). This action is mediated via interaction with LRP, which contributes physiologically to the selective uptake of HDL cholesteryl ester in adipocytes.…”

Trophoblast‐like human choriocarcinoma cells serve as a suitable in vitro model for selective cholesteryl ester uptake from high density lipoproteins

“…Also in mice with a targeted deletion of the LDL-receptor gene, the up-regulation of selective CEuptake suggests that SR-BI can compensate for the loss of LDL-receptor function [58]. Recently, the LDL-receptor related protein has also been addressed to mediate, at least in part, selective lipid uptake [59]. LDL-receptor related protein was found to be associated with syncytiotrophoblasts (but not cytotrophoblasts) and BeWo cells [10].…”

Insect lipoprotein follows a transferrin-like recycling pathway that is mediated by the insect LDL receptor homologue

“…It has been suggested that specific mammalian tissues may selectively take up lipoprotein-bound components with LDLR homologous receptors (e.g. LRP), however, without endocytosis of the ligand (Vassiliou et al, 2001;Swarnakar et al, 2001). Additionally, alternative functions for LDLR that deviate from the classic lysosomal lipoprotein delivery could also depend on the developmental stage or type of tissue (Dehouck et al, 1997).…”