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Journal of Lipid Research, Vol 31, 1361-1369, Copyright © 1990 by Lipid Research, Inc.
HF Zhang, HJ Basra and UP Steinbrecher
Oxidative modification of low density lipoproteins (LDL) has been shown to
cause accelerated degradation of LDL via the scavenger receptor pathway in
cultured macrophages, and it has been proposed that this process might lead
to cholesterol accumulation in macrophages in the arterial wall in vivo.
However, oxidation of LDL is accompanied by a substantial reduction in LDL
total cholesterol content and hence the amount of cholesterol delivered by
oxidatively modified LDL may be less than that delivered by scavenger
receptor ligands such as acetyl LDL which results in massive cholesterol
accumulation in cultured macrophages. The present studies were done to
determine whether the decrease in total cholesterol content during LDL
oxidation was due to oxidation of cholesterol and cholesteryl ester, and to
determine whether the resulting oxidized sterols could affect cholesterol
esterification in cultured macrophages. It was found that when LDL
prelabeled with [3H]cholesteryl linoleate was oxidized, there was a
decrease in cholesterol mass but no change in radioactivity. The
radioactive substances derived from cholesteryl linoleate appeared more
polar than the parent compound when analyzed by reverse-phase liquid
chromatography, but were not identical with free cholesterol. Thin- layer
chromatography of oxidized LDL lipids confirmed the loss of esterified
cholesterol, and revealed multiple new bands, some of which matched
reference oxysterols including 7-ketocholesterol, 5,6- epoxycholesterol,
and 7-hydroxycholesterol. In addition to oxysterols, oxidized cholesteryl
esters were also present. Quantitation by gas chromatography indicated that
7-ketocholesterol was the major oxysterol present.(ABSTRACT TRUNCATED AT
250 WORDS)
ARTICLES
Effects of oxidatively modified LDL on cholesterol esterification in cultured macrophages
Department of Medicine, University of British Columbia, Vancouver, Canada.
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