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Journal of Lipid Research, Vol 30, 1055-1064, Copyright © 1989 by Lipid Research, Inc.
T Mazzone, K Basheeruddin and C Poulos
The relationship between macrophage cholesterol content and apolipoprotein
E (apoE) gene expression was investigated in cultured mouse peritoneal
macrophages. Acetylated low density lipoprotein (ALDL) at 25 micrograms/ml
led to increased macrophage messenger RNA abundance as detected by Northern
blot hybridization. Incubation in a range of ALDL concentrations (0-100
microgram/ml) led to graded increases in macrophage free and esterified
cholesterol, and apoE mRNA detected by slot blot hybridization. After a 2-h
pulse of ALDL, with or without acyl-CoA:cholesterol acyltransferase
inhibition, increased apoE mRNA was not detected until after 6 h. Removal
of cholesterol from upregulated macrophages, using human high density
lipoprotein, resulted in a return of apoE mRNA levels toward baseline.
Nuclear run-off transcription assays demonstrated increased apoE gene
transcription in macrophages incubated with ALDL. It is concluded that: a)
previously reported changes in macrophage apoE content and secretion after
cholesterol enrichment or depletion can be attributed to changes in apoE
mRNA levels; and b) cholesterol-induced changes in apoE mRNA are associated
with increased apoE gene transcription.
ARTICLES
Regulation of macrophage apolipoprotein E gene expression by cholesterol
Department of Medicine, Michael Reese Hospital, University of Chicago, IL 60637.
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