Cholesterol esterification is not essential for secretion of lipoprotein components by HepG2 cells.
Hepatic acyl CoA:cholesterol acyltransferase (ACAT) activity may determine storage of cholesterol and supply of cholesteryl esters for the neutral lipid core of very low density lipoprotein. Inhibition of cholesterol esterification in HepG2 cells, by the ACAT inhibitor 447C88, partially reduced the secretion of labelled total cholesterol, but the secretion of apoprotein B mass, and of radiolabelled triacylglycerol and phosphatidylcholine were unaffected. Furthermore, this compound was shown to substantially deplete the intracellular cholesteryl ester mass without affecting secretion of lipoprotein components. In contrast, the less potent ACAT inhibitor, CL277,082, significantly decreased secretion of labelled triacylglycerol, phosphatidylcholine and total cholesterol, in a manner which mirrored the decreases in secretion of apoB. This study clearly illustrates that ACAT inhibitors can exert differential 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.
Graham
A
A
Biology Division, Wellcome Research Laboratories, Beckenham, Kent, UK.
Wood
J L
JL
Russell
L J
LJ
D000924:Anticholesteremic Agents / Q000494:pharmacology; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004951:Esterification; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured
C093460:447C88; D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D010671:Phenylurea Compounds; D010713:Phosphatidylcholines; D014280:Triglycerides; D019301:Oleic Acid; C007997:25-hydroxycholesterol; C050492:CL 277082; D002784:Cholesterol; D002785:Sterol O-Acyltransferase