AJP - Cell Physiology, Vol 271, Issue 6 C1879-C1886, Copyright © 1996 by American Physiological Society
Ibuprofen protects human endothelial cell prostaglandin H synthase from hydrogen peroxide
D. A. Wessels and S. L. Hempel
Department of Veterans Affairs Medical Center, University of Iowa, Iowa City 52242, USA.
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 anti-inflammatory 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. 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.
