Oxidized LDL increase free cholesterol and fail to stimulate cholesterol esterification in murine macrophages.
Oxidatively modified low density lipoproteins (Ox-LDL) may be involved in determining the formation of foam cells by inducing cellular cholesteryl ester accumulation. We studied the effect of copper oxidized LDL (Ox-LDL) on cholesterol accumulation and esterification in murine macrophages. Ox-LDL (44 micrograms/ml of lipoprotein cholesterol) increased the total cholesterol content of the cells from 29 to 69 micrograms/mg cell protein. Free cholesterol accounted for 85% of this increase. Acetyl LDL (Ac-LDL) (38 micrograms/ml of lipoprotein cholesterol), raised total cellular cholesterol content to a similar extent (76 micrograms/mg cell protein), however only 25% of the accumulated cholesterol was unesterified. When ACAT activity was determined after incubation of J774 cell with Ox- or Ac-LDL, Ox-LDL were 12 times less effective than Ac-LDL in stimulating cholesteryl ester formation. This was not due to an inhibition of ACAT by Ox-LDL since these lipoproteins failed to inhibit pre activated enzyme in cholesteryl ester-loaded macrophages. The uptake of 125I-Ox-LDL: was 175% that of 125I-Ac-LDL, while degradation was only 20%. All together these data suggest an altered intracellular processing of Ox-LDL, which may be responsible for free cholesterol accumulation.
Roma
P
P
Institute of Pharmacological Sciences, University of Milan, Italy.
Catapano
A L
AL
Bertulli
S M
SM
Varesi
L
L
Fumagalli
R
R
Bernini
F
F
D000107:Acetylation; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D010529:Peritoneal Cavity / Q000166:cytology
D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D002784:Cholesterol