Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) by the liver. LPL promotes this selective lipi d uptake independent of lipolysis. In this study, the role of SR-BI in the mechanism of this LPL-mediated increase in selective CE uptake was explored . Baby hamster kidney (BHK) cells were transfected with the SR-BI cDNA, and significant SR-BI expression could be detected in immunoblots, whereas no SR-BI was visualized in control cells. Y1-BS1 murine adrenocortical cells w ere cultured without or with adrenocorticotropic hormone, and cells with no detectable or with SR-BI were obtained. These cells incubated without or w ith LPL in medium containing I-125/[H-3]cholesteryl oleyl ether-labeled HDL 3; tetrahydrolipstatin inhibited the catalytic activity of LPL. In BHK and in Y1-BS1 cells without or with SR-BI expression, apparent HDL3 selective C E uptake ([H-3]CEt - I-125) was detectable. Cellular SR-BI expression promo ted HDL3 selective CE uptake by similar to 250-1,900%. In BHK or YI-BSI cel ls, LPL mediated an increase in apparent selective CE uptake. Quantitativel y, this stimulating LPL effect was very similar in control cells and in cel ls with SR-BI expression. The uptake of radiolabeled HDL3 was also investig ated in human embryonal kidney 293 (HEK 293) cells that are an established SR-BI-deficient cell model. LPL stimulated [H-3]cholesteryl oleyl ether upt ake from labeled HDL3 by HEK 293 cells substantially, showing that LPL can induce selective CE uptake from HDL3 independent of SR-BI. To explore the r ole of cell surface proteoglycans on lipoprotein uptake, we induced proteog lycan deficiency by heparinase treatment. Proteoglycan deficiency decreased the LPI-mediated promotion of HDL3 selective CE uptake. In summary, eviden ce is presented that the stimulating effect of LPL on HDL3 selective CE upt ake is independent of SR-BI and lipolysis. However, cell surface proteoglyc ans are required for the LPL action on selective CE uptake. It is suggested that pathways distinct from SR-BI mediate selective CE uptake from HDL.