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Journal of Lipid Research, Vol. 44, 1020-1032, May 2003
Copyright © 2003 by Lipid Research, Inc.

Hepatic lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent from SR-BI

May Brundert^*, Joerg Heeren, Heiner Greten^* and Franz Rinninger^1,*

^* Universitaetsklinikum Hamburg-Eppendorf, Department for Internal Medicine, Martinistrasse 52, 20246 Hamburg, Germany
Department of Molecular Cell Biology, Martinistrasse 52, 20246 Hamburg, Germany

¹ To whom correspondence should be addressed. e-mail: rinninger{at}uke.uni-hamburg.de

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) by the liver. Hepatic lipase (HL) promotes this lipid uptake independent from lipolysis. The role of SR-BI in this HL-mediated increase in 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. These cells were 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 cell types, 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. These results suggest that HL promotes selective uptake independent from SR-BI. To investigate the role of cell surface proteoglycans on the HL-mediated HDL₃ uptake, proteoglycan deficiency was induced by heparinase digestion. Proteoglycan deficiency decreased the HL-mediated promotion of selective CE uptake.

In summary, the stimulating HL effect on HDL selective CE uptake is independent from SR-BI and lipolysis. 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.

Abbreviations: ¹²⁵I-TC, radioiodinated tyramine cellobiose ligand; [³H]CEt, [³H]cholesteryl oleyl ether; BHK, baby hamster kidney; CE, cholesteryl ester; HDL, high density lipoprotein (d = 1.063–1.21 g/ml); HDL₃, high density lipoprotein₃ (d = 1.125–1.21 g/ml); HEK 293, human embryonal kidney 293; HL, hepatic lipase; LPDS, lipoprotein-deficient serum; LPL, lipoprotein lipase; SR-BI, scavenger receptor class B type I; THL, tetrahydrolipstatin

Supplementary key words scavenger receptor class B type I • tetrahydrolipstatin • radioiodinated tyramine cellobiose ligand

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