Heparan sulphate proteoglycans are involved in the lipoprotein lipase-mediated enhancement of the cellular binding of very low density and low density lipoproteins.
We found that LPL enhances the binding to HepG2 cells and fibroblasts of both VLDL and apoE free LDL. In the presence of 1.7 micrograms/ml of purified bovine LPL, the binding of LDL and VLDL was up to 60 fold increased as compared to the control binding. In addition, LPL enhances the binding in LDL-receptor negative fibroblasts to the same extent as it does in normal fibroblasts. The presence of 10 mM of EGTA could not prevent the LPL-mediated enhancement of the binding of both LDL and VLDL to fibroblasts, indicating that the binding is calcium independent. Furthermore, up- and down regulation of the LDL receptor did not influence the binding of these lipoproteins in the presence of LPL. Strikingly, we found that the enhancing effect of LPL on the binding of LDL and VLDL to HepG2 cells could be abolished by preincubation of the cells with heparinase, suggesting that heparan sulphate proteoglycans are involved in the LPL-mediated stimulation. We hypothesize that the enhancement of the cellular binding of LDL and VLDL in the presence of LPL is caused by an LPL-bridging between proteoglycans present on the plasma membrane and the lipoproteins, and that the LDL receptor and LRP are not involved.
Mulder
M
M
Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands.
Lombardi
P
P
Jansen
H
H
van Berkel
T J
TJ
Frants
R R
RR
Havekes
L M
LM
D002462:Cell Membrane / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011509:Proteoglycans / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008071:Lipoprotein Lipase; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011509:Proteoglycans; D011971:Receptors, Immunologic; D011973:Receptors, LDL