Ibuprofen protects human endothelial cell prostaglandin h synthase
from hydrogen peroxide.
Wessels, Duane A., and Stephen L. Hempel.
Department of Veterans Affairs Medical Center and Department of
Medicine, University of Iowa, Iowa City, Iowa 52242
APStracts 3:0211C, 1996.
Human endothelial cells exposed to H2O2 demonstrate decreased
prostacyclin (PGI2) synthesis due to decreased prostaglandin H
synthase (PGH synthase) activity. We tested the hypothesis that PGH
synthase activity could be protected from H2O2 by a reversible
nonsteroidal antiinflammatory drug. Experiments demonstrate that
ibuprofen, if present during H2O2 exposure, protects endothelial cell
PGH synthase against the decrease in prostaglandin formation caused
by H2O2. Additional studies demonstrated that decreasing arachidonic
acid release from cell phospholipids during H2O2 exposure did not
protect PGI2 synthesis following H2O2 exposure. In other experiments,
ibuprofen did not chelate Fe2+ in a conformation that inhibited the
reactivity of Fe2+. In addition, ibuprofen did not scavenge HO x .
However, we demonstrate that ibuprofen significantly protects
purified PGH synthase cyclooxygenase activity from the effects of
H2O2. The results confirm the hypothesis. These findings suggest that
ibuprofen displaces oxidant species from the cyclooxygenase site of
PGH synthase, thereby preventing oxidation of the functional groups
important for PGH synthase activity.
Received 3 April 1996; accepted in final form 19 June 1996.
APS Manuscript Number C188-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96