Active taurocholic acid flux through hepatoma cells increases the cellular pool of unesterified cholesterol derived from lipoproteins.
The effect of bile acid flux on the fate of lipoprotein-derived cholesterol was studied in bile acid-transporting McNtcp.18 hepatoma cells. The intracellular unesterified cholesterol (UC) concentration rose when McNtcp.18 cells grown in the presence of either high density lipoproteins (HDL) or low density lipoproteins (LDL) were incubated with taurocholic acid (TCA). This effect was more pronounced when the exogenous source of cholesterol was HDL. The presence of TCA in the culture medium of McNtcp.18 cells had no discernible effect on the uptake of cholesteryl esters (CE) from either lipoprotein. TCA treatment of cells preincubated with either lipoprotein did not affect cholesterol synthesis but antagonized the stimulation of cholesterol esterification in cells that were incubated with LDL. The CE concentration in cells treated with TCA was decreased, relative to cells not incubated with TCA, suggesting that cellular CE stores were also hydrolyzed. The TCA treatment reduced the amount of total cholesterol released into the medium by the lipoprotein-treated cells, which was coincident with the reduction in the amount of apolipoprotein B in the culture medium. However, the proportion of UC released into the medium by the lipoprotein-treated cells was increased in cells capable of active bile acid transport. The results indicate that active bile acid flux through hepatoma cells increases the cellular pool of UC derived from lipoproteins. The UC released by the cells into the culture medium under this condition may represent cholesterol destined for direct biliary secretion.
Li
Q
Q
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Yokoyama
S
S
Agellon
L B
LB
D000818:Animals; D001693:Biological Transport, Active; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D013656:Taurocholic Acid / Q000494:pharmacology*; D014316:Tritium; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002788:Cholesterol Esters; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014316:Tritium; D013656:Taurocholic Acid; D002784:Cholesterol