Impaired capacity of acute-phase high density lipoprotein particles to deliver cholesteryl ester to the human HUH-7 hepatoma cell line.
The major role of native high density lipoprotein (HDL) is to carry cholesterol from peripheral tissues to the liver for bile excretion. As acute-phase (AP)-HDL has a decreased ability for cellular cholesterol efflux but an increased capacity for cholesteryl ester (CE) delivery to peripheral tissues, the interaction of AP-HDL with human hepatoma cells was studied. Binding studies to HUH-7 cells revealed saturable binding properties for HDL and AP-HDL at 4 degrees C. At 37 degrees C, specific cell-association of (125)I- and [1,2,6,7-(3)H]-cholesteryl palmitate ([(3)H]CE)-labeled lipoprotein particles was 2.2- and 1.6-fold higher for HDL indicating that total CE delivery was significantly (P<0.05) higher for HDL in comparison to AP-HDL. In parallel, selective CE uptake (the difference between total lipid uptake and holoparticle uptake) from AP-HDL was decreased compared with HDL. The fact that the capacity for cellular cholesterol efflux from HUH-7 cells is slightly impaired by AP-HDL (compared with HDL) is of support that scavenger receptor class B, type I (SR-BI), the only receptor so far known to mediate bi-directional lipid flux, might be involved in altered HUH-7 cholesterol hemostasis by AP-HDL. Our in vitro findings suggest that HDL and AP-HDL interact differently with cells of hepatic origin resulting in decreased hepatic cholesterol removal from the circulation during the AP reaction.
Artl
Andreas
A
Institute of Medical Biochemistry and Molecular Biology, Karl-Franzens University Graz, Harrachgasse 21, A-8010 Graz, Austria.
Marsche
Gunther
G
Pussinen
Pirkko
P
Knipping
Gabriele
G
Sattler
Wolfgang
W
Malle
Ernst
E
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001693:Biological Transport, Active; D006528:Carcinoma, Hepatocellular; D002462:Cell Membrane / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D010316:Particle Size; D011485:Protein Binding; D011817:Rabbits; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL