Association of hepatic lipase with proteoglycans stimulates the production of proteoglycans in vivo and in vitro.
HL is synthesized in hepatocytes and functions while bound to heparan sulfate proteoglycans (HSPGs) in sinusoidal endothelial cells. The HL-mediated uptake of lipoprotein requires cell-surface HSPG. The present study tested whether HL plays a role in the production of HSPG. The production of HSPG in Chinese hamster ovary (CHO) cells was determined by measuring the incorporation of (35)SO(4) into PGs. HL-producing HL-CHO cells showed approximately 30% more cellular PG than did wild-type (WT) cells. In contrast, PG production in cells producing a membrane-anchored HL-glycophosphatidylinositol (GPI) that was not bound to HSPG was virtually identical to that in WT cells. When purified HL was added to the WT- or HL-GPI cells, PG production increased significantly to a level similar to that of the HL-secreting cells, suggesting that the binding of HL to HSPG triggered the increased HSPG production. Heparin reduced PG production in HL-producing cells, confirming that PG production is stimulated only when HL is present as a ligand for HSPG. Real-time PCR and Northern blots demonstrated that PG production was significantly reduced in animals lacking HL. Together, these data suggest that the binding of HL to PG on the cell surface exerts a positive feedback on cellular PG production.
Lee
Sung-Joon
SJ
Stanford University, CA 94305, USA.
Kadambi
Sujata
S
David
Christopher
C
Cooper
Allen D
AD
Choi
Sungshin Y
SY
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000187:drug effects; D017261:Glycosylphosphatidylinositols; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis*; D006493:Heparin / Q000494:pharmacology; D008024:Ligands; D008049:Lipase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding; D051381:Rats; D013462:Sulfur Radioisotopes / Q000378:metabolism; D014162:Transfection
D017261:Glycosylphosphatidylinositols; D019812:Heparan Sulfate Proteoglycans; D008024:Ligands; D013462:Sulfur Radioisotopes; D006493:Heparin; D008049:Lipase