HEPARAN SULFATE-DEPENDENT AND LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN-DEPENDENT CATABOLIC PATHWAYS FOR LIPOPROTEIN-LIPASE IN MOUSEEMBRYONIC FIBROBLASTS

Heparan sulfate and low density lipoprotein receptor related protein ( LRP) have been shown to participate in the uptake and degradation of t he enzyme lipoprotein lipase (LPL). Yet, the contribution of each of t hese pathways to LPL metabolism and their possible dependence is unkno wn. In the present study we examined the metabolism of I-125-labeled L PL in untreated and heparinase-treated primary wild-type mouse embryon ic fibroblasts (MEF) and in mouse fibroblasts that express single LRP allele (PEA-10) or are lacking the LRP (PEA-13). The degradation of LP L in PEA-13 cells was 30% lower than in MEF and PEA-10 cells. Heparina se treatment decreased the LPL degradation by 58%, 79% and 92%, wherea s heparin reduced such degradation by 87%, 90% and 94% in MEF, PEA-10 and PEA-13 cultures, respectively. Assuming that a) heparinase treatme nt abolished the heparan-sulfate pathway, and that b) the degradation remaining in heparin-treated cultures represents nonspecific values, i t appears that heparan sulfate contributes about 61%, 83% and 95% of t otal LPL degradation, whereas the LRP pathway contributes 39%, 17% and less than 5% of LPL degradation in MEF, PEA-10 and PEA-13 cells, resp ectively. In addition, the data indicate that LPL interaction with hep aran sulfate and the LRP pathways is independent of each other. The st udy shows that these cells possess both a heparan sulfate-dependent pa thway and an LRP-dependent pathway for LPL metabolism and that the two pathways are independent of each other.