Binding to heparan sulfate is a major event during catabolism of lipoprotein lipase by HepG2 and other cell cultures.
Lipoprotein lipase (LPL) is rapidly and efficiently cleared from the circulation by the liver through an as yet unclear mechanism. In the present study, we determined the nature of LPL interactions with the liver parenchimal cell line HepG2 as compared to other cells in culture. Binding, cell association and degradation of 125I-labelled bovine milk LPL by HepG2 cells, normal and low density lipoprotein (LDL) receptor-negative human fibroblasts and Chinese hamster ovary (CHO) cells show similar values irrespective of source and origin. LPL metabolism in HepG2 cells was characterized by a high capacity to degrade the enzyme, an extremely high sensitivity to heparin and was inhibited by 60%-70% after treatment of the cells with sodium chlorate and heparinase (but not chondroitinase). These findings suggested an important role for heparan sulfate in the process of cell interaction and metabolism of LPL. To further clarify the role of heparan sulfate in determining the LPL-cell interactions, we compared the metabolism of LPL in wild type and mutant heparan sulfate-deficient CHO cells. Heparan sulfate-deficient CHO cells show a low capacity to bind and degrade LPL, about 10%-20% that of the wild type cells. In another set of experiments, we sought to determine whether LPL interactions with HepG2 cells are affected by triglyceride-rich lipoproteins. The results clearly show that whereas unlabeled LPL dramatically enhanced the metabolism of radioiodinated very low density lipoprotein (VLDL), unlabeled VLDL had no effect on radioiodinated LPL metabolism in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Sehayek
E
E
Institute of Lipid and Atherosclerosis Research, Haim Sheba Medical Center, Tel Hashomer, Israel.
Olivecrona
T
T
Bengtsson-Olivecrona
G
G
Vlodavsky
I
I
Levkovitz
H
H
Avner
R
R
Eisenberg
S
S
D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding
D006493:Heparin; D006497:Heparan Sulfate; D008071:Lipoprotein Lipase; D008079:Lipoproteins, VLDL