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Journal of Lipid Research, Vol 31, 551-565, Copyright © 1990 by Lipid Research, Inc.
HF Zhang, WB Davis, XS Chen, KH Jones, RL Whisler and DG Cornwell
The role of oxidized plasma lipoproteins in modifying arachidonic acid (AA)
metabolism was studied in smooth muscle cells (SMC). Very low density
lipoproteins (VLDL), unoxidized low density lipoproteins (LDLBHT) isolated
with butylated hydroxytoluene (BHT), and oxidized LDL (LDLOXID) were
separated from human serum. Thiobarbituric acid reactant (TBAR) levels were
adjusted by saline incubations. Prostanoids in guinea pig SMC cultures were
measured either by radioimmunoassay (RIA) or the isolation by high
performance liquid chromatography (HPLC) of labeled prostanoids from SMC
prelabeled with [14C]AA. Cell morphology and viability were studied by
staining with Giemsa, nile red, and propidium iodide. VLDL and LDLBHT had
little effect on prostanoid synthesis. Low-TBAR-LDLOXID enhanced total
prostanoid levels and diminished the release of labeled prostanoids.
Similar effects were found with exogenous free AA (unlabeled).
Low-TBAR-LDLOXID did not affect the release of endogenous phospholipid AA
as free AA. Synergism occurred between LDLOXID and exogenous free AA in
prostanoid synthesis. Low-TBAR-LDLOXID evidently enhanced prostanoid levels
in SMC both by supplying AA and by stimulating cyclooxygenase.
High-TBAR-LDLOXID blocked prostanoid synthesis and enhanced cell death but
time and pulse- recovery experiments showed that these effects were
unrelated. High- TBAR-LDLOXID stimulated prostanoid synthesis when BHT was
added to the incubation media. High-TBAR-LDLOXID also caused massive free
AA release and the formation of many nonprostanoid derivatives.
High-TBAR-LDLOXID evidently diminished overall prostanoid levels in SMC by
inhibiting cyclooxygenase and at the same time stimulating AA release and
the formation of other AA derivatives.
ARTICLES
Effects of oxidized low density lipoproteins on arachidonic acid metabolism in smooth muscle cells
Department of Physiological Chemistry, Ohio State University, Columbus 43210.
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