Abstract

Lipoprotein lipase (LPL), the major enzyme responsible for the hydrolysis of triglycerides, is primarily synthesized by adipocytes and myocytes. In addition to synthesis, degradation of cell surface-associated LPL is thought to be important in regulating production of the enzyme. We studied LPL metabolism in the LPL synthesizing adipocyte cell line BFC-1 beta and assessed the contributions of cell surface heparan sulfate proteoglycans (HSPG), low density lipoprotein receptor related protein (LRP), and glycosylphosphatidylinositol (GPI)-linked proteins to LPL uptake and degradation by these cells. Adipocytes degraded 10-12% of total cell surface I-labeled LPL in 2 h and 23-28% in 4 h. In 1 h, 30-54% of the degradation was inhibited by the 39 kDa receptor associated protein (RAP), an inhibitor of ligand binding to LRP. At 4 h, only 19-23% of the LPL degradation was RAP inhibitable. This suggested that two pathways with different kinetics were important for LPL degradation. Heparinase/heparitinase treatment of cells showed that most LPL degradation required the presence of HSPG. Treatment with phosphatidylinositol-specific phospholipase C (PIPLC) inhibited 125I-labeled LPL degradation by 13%. However, neither RAP nor PIPLC treatment of adipocytes significantly increased the amount of endogenously produced LPL activity in the media. To determine whether direct uptake of LPL bound to HSPG could account for the non-RAP sensitive LPL uptake and degradation, proteoglycan metabolism was assessed by labeling cells with 35SO4. Of the total pericellular proteoglycans, 14% were PIPLC releasable; surprisingly, 30% were dissociated from the cells with heparin. The amount of labeled pericellular proteoglycans decreased 26% in 2 h and 50% in 8 h, rapid enough to account for at least half of the degradation of cell surface LPL. We conclude that adipocytes degrade a fraction of the cell surface LPL, and that this process is mediated by both proteoglycans and RAP-sensitive receptors.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.