Scavenger receptor class B, type I on non-malignant and malignant human epithelial cells mediates cholesteryl ester-uptake from high density lipoproteins.
Hepatoma cell lines serve as a suitable model to study hepatic clearance of lipoprotein-associated cholesteryl esters (CEs). The present study aimed at investigating holoparticle-association of and selective CE-uptake from human high density lipoprotein subclass 3 (HDL3) by non-malignant adult (Chang-liver) and non-malignant fetal (WRL-68) epithelial cell lines as well as a hepatocellular carcinoma (HUH-7) cell line. Binding properties of 125I-HDL3 at 4 and 37 degrees C were similar for all three cell lines while degradation rates were highest for Chang-liver cells. Calculating the selective uptake of HDL3-associated CEs as the difference between [3H]CE- and 125I-HDL3 cell-association revealed that the selective lipid uptake and holoparticle-association was similar in Chang-liver while in WRL-68 and HUH-7 cells pronounced capacity for lipid tracer uptake in excess of holoparticle uptake was measured. Using RT-PCR, Northern and Western blot analysis, as well as immunocytochemical technique pronounced expression of scavenger receptor class B, type I (SR-BI) but not SR-BII (a splice variant of SR-BI less efficient for selective CE-uptake than SR-BI) could be identified in HUH-7 and WRL-68 cells. A polyclonal antiserum raised against SR-BI significantly decreased cell-association of [3H]CE-HDL3 in HUH-7 and WRL-68. The present findings suggest that the capacity for selective cholesteryl ester-uptake from high density lipoprotein by malignant and normal epithelial cells from the liver depends on expression of the scavenger receptor class B, type I.
Wadsack
Christian
C
Institute of Medical Biochemistry and Molecular Biology, Karl-Franzens University Graz, Harrachgasse 21, A-8010, Graz, Austria.
Hirschmugl
Birgit
B
Hammer
Astrid
A
Levak-Frank
Sanja
S
Kozarsky
Karen F
KF
Sattler
Wolfgang
W
Malle
Ernst
E
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D006224:Cricetinae; D004847:Epithelial Cells / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins; D014407:Tumor Cells, Cultured
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins