The effects of lipid peroxidation on rabbit aortic endothelial cell ph
ospholipid turnover was studied using linoleic acid hydroperoxide (LOO
H). Following treatments with 20-40 mu M LOOH, cells prelabeled with e
ither arachidonic acid (20:4) or oleic acid (18:1) showed a movement o
f these fatty acids out of the phospholipids and into neutral lipid an
d free fatty acid pools. There was also a release of radioactive free
fatty acids and phospholipids into the media, which was significantly
increased as compared to cells maintained under standard culture condi
tions. Fatty acid uptake and distribution among phospholipid pools was
also affected by LOOH treatment where incorporation of 20:4 and 18:1
into phosphatidylcholine (PC) decreased, while uptake into phosphatidy
linositol (PI) increased after 1 h of incubation with 40 mu M LOOH. Th
ese effects were also inhibited by vitamin E. In cells prelabeled with
20:4 or 18:1 under conditions where approximately 99% of the fatty ac
ids were incorporated into neutral and phospholipid pools, LOOH treatm
ent produced a decrease in radioactivity associated with PC, while the
specific activity of PI increased. The extent of these changes was gr
eater for 20:4 than 18:1. but in each case the effects were inhibited
by Vitamin E. The temporal pattern of uptake for labeled choline and i
nositol after LOOH treatments paralleled those found for fatty acid in
corporation. These cell responses indicate that induction of lipid per
oxidation produces rapid fatty acid release and phospholipid turnover
involving repair as well as de novo synthesis. The implications of the
se effects on turnover of specific phospholipids and cell responses to
oxidative stress are discussed.