Down-regulation of hormone-sensitive lipase in sterol ester-laden J774.2 macrophages.
The development of atherosclerotic plaques in arteries is a key step in atherogenesis, with cholesterol ester accumulation in macrophage-derived foam cells being recognized as a major pathogenic event in this process. In this study, the mouse macrophage cell line J774.2 was induced to accumulate intracellular sterol esters by incubation with 25-hydroxycholesterol in the presence of oleic acid. The accumulation of sterol esters in these cells was found to be accompanied by a marked decrease in the activity of the enzyme responsible for their hydrolysis, namely hormone-sensitive lipase (HSL); Western blotting studies revealed a corresponding decrease in the levels of the HSL polypeptide. Similar findings were obtained after incubation with oxidized low-density lipoprotein or very-low-density lipoprotein. These findings suggest that down-regulation of the expression of HSL is important in cholesterol ester accumulation in macrophages.
Jepson
C A
CA
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, UK.
Harrison
J A
JA
Kraemer
F B
FB
Yeaman
S J
SJ
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism*
D002788:Cholesterol Esters; D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D009829:Oleic Acids; C099252:oxidized low density lipoprotein; D019301:Oleic Acid; C007997:25-hydroxycholesterol; D002787:Sterol Esterase