Interaction of LDL and Lp[a] with human skin fibroblasts.
We have studied the interaction of LDL and Lp[a] with fibroblasts. Our studies suggest that Lp[a] does not effectively compete with LDL for binding to the LDL receptor, and does not efficiently suppress the activity of the intracellular enzyme HMG-CoA reductase. However, Lp[a-], formed by reduction of the disulfide bond between apo[a] and apoB, behaves much like homologous LDL, whether or not apo[a] is removed from the mixture, and in spite of the fact that one or more apoB disulfides may also have been cleaved. In our studies we also noted that Lp[a] often enhanced binding of 125I-LDL by fibroblasts. Further investigation has suggested that this interaction is time-dependent. Experiments in receptor-negative fibroblasts indicate that the enhancement is not related to the presence of the LDL receptor; however, it is inhibited by the removal of calcium from the medium. The presence of sialic acid at millimolar concentrations in the medium inhibits much of the Lp[a]-enhanced binding of 125I-LDL to the cells. These studies suggest that Lp[] may in some way enhance LDL binding to cells, perhaps via interaction with cell surface glycosaminoglycans or proteoglycans or with collagen.
Mims
M P
MP
Department of Medicine, Baylor College of Medicine, Houston, TX.
Gaubatz
J W
JW
Ghazzaly
K K
KK
Via
D P
DP
Clough
D S
DS
Morrisett
J D
JD
D001053:Apolipoproteins / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D053241:Apoprotein(a); D001667:Binding, Competitive; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D012867:Skin / Q000378:metabolism
D001053:Apolipoproteins; D001055:Apolipoproteins B; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D012794:Sialic Acids; D006903:Hydroxymethylglutaryl CoA Reductases; D053241:Apoprotein(a); D019158:N-Acetylneuraminic Acid; D002118:Calcium