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Papers In Press, published online ahead of print March 1, 2003
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Internal Medicine, University of Hamburg-Eppendorf, Hamburg 20251
Corresponding Author: rinninger{at}uke.uni-hamburg.de
SR-BI mediates the selective uptake of HDL cholesteryl esters (CE) by the liver. Hepatic lipase (HL) promotes this lipid uptake independent from lipolysis. The role of SR-BI in this HL-mediated increase in HDL selective CE uptake was explored. Baby hamster kidney (BHK) cells were transfected with the SR-BI cDNA yielding cells with SR-BI expression whereas no SR-BI was detected in control cells (vector). These cells incubated in medium containing 125I/[3H]cholesteryl oleyl ether-labeled HDL3 (d = 1.125-1.21 g/ml) and HL was absent or present; tetrahydrolipstatin (THL) blocked lipolysis. In control BHK cells and in BHK cells with SR-BI, HDL3 selective CE uptake ([3H] – 125I) was detectable and SR-BI promoted this uptake. In both types of BHK cells, HL mediated an increase in selective CE uptake from HDL3. Quantitatively this HL effect was similar in control BHK cells and in BHK cells with SR-BI. The HL action on HDL3 uptake was explored in human embryonal kidney 293 (HEK 293) cells which lack SR-BI. HL stimulated [3H]cholesteryl oleyl ether uptake from HDL3 by HEK 293 cells. These results suggest that HL promotes selective CE uptake independent from SR-BI. Immunofluorescence revealed that (a) SR-BI expression did not modify the cellular HL binding and (b) SR-BI and HL predominantly localize in distinct regions of the plasma membrane. To investigate the role of cell surface proteoglycans on the HL-mediated HDL3 uptake, proteoglycan deficiency was induced by heparinase treatment. Proteoglycan deficiency of BHK cells decreased the HL-mediated promotion of selective CE uptake. In summary, the stimulating HL effect on HDL3 selective CE uptake is independent from SR-BI and independent from lipolysis. Cell surface proteoglycans are a requisite for the HL action on selective uptake. Results suggest that (a) pathway(s) distinct from SR-BI mediate(s) selective CE uptake from HDL.
Revised on February 20, 2003
Accepted on February 20, 2003
Hepatic lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent from scavenger reseptor class B type I (SR-BI)
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