A. Graham et al., CHOLESTEROL ESTERIFICATION IS NOT ESSENTIAL FOR SECRETION OF LIPOPROTEIN COMPONENTS BY HEPG2 CELLS, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1302(1), 1996, pp. 46-54
Hepatic acyl CoA:cholesterol acyltransferase (ACAT) activity may deter
mine storage of cholesterol and supply of of cholesteryl esters for th
e neutral lipid core of very low density lipoprotein. Inhibition of ch
olesterol esterification in HepG2 cells, by the ACAT inhibitor 447C88,
partially reduced the secretion of labelled total cholesterol, but th
e secretion of apoprotein B mass, and of radiolabelled triacylglycerol
and phosphatidylcholine were unaffected. Furthermore, this compound w
as shown to substantially deplete the intracellular cholesteryl ester
mass without affecting secretion of lipoprotein components. In contras
t. the less potent ACAT inhibitor, CL277,082, significantly decreased
secretion of labelled triacylglycerol, phosphatidylcholine and total c
holesterol, in a manner which mirrored the decreases in secretion of a
poB. This study clearly illustrates chat ACAT inhibitors can exert dif
ferential effects on secretion of apoB-containing lipoproteins, which
do not correlate with their efficacy in inhibiting ACAT, arguing that
cholesterol esterification is not essential for Lipoprotein secretion
From these cells.