AJP - Cell Physiology, Vol 264, Issue 6 C1448-C1457, Copyright © 1993 by American Physiological Society
Effect of glutathione on endothelial prostacyclin synthesis after anoxia
S. L. Hempel, D. A. Wessels and A. A. Spector
Department of Veterans Affairs Medical Center, Iowa City, Iowa.
We previously observed decreased prostacyclin (PGI2) formation after
reoxygenation of anoxic endothelium. In the present study, the effects of
glutathione on endothelial prostaglandin (PG) H synthase activity after
reoxygenation were explored. Intracellular glutathione content decreased
70% after 24 h of anoxia; reoxygenation did not produce any additional
decrease in glutathione content. Intracellular glutathione was maintained
in the reduced state by the endothelium even during the oxidant stress
caused by reoxygenation or the addition of peroxide. Glutathione depletion
produced by DL-buthionine-(S,R)-sulfoximine (BSO),
1,3-bis(chloroethyl)1-nitrosourea (BCNU), or incubation in a
sulfhydryl-free medium resulted in increased sensitivity of PGH synthase to
the effects of added H2O2. However, glutathione depletion resulting from
BSO or culture in sulfhydryl-free medium during anoxia did not increase the
sensitivity of PGH synthase to reoxygenation. In addition, anoxia did not
make the endothelium more sensitive to H2O2. Glutathione peroxidase and
glutathione reductase activities were preserved after anoxia-reoxygenation.
When glutathione reductase was inhibited with BCNU during reoxygenation,
PGI2 release was decreased further. These findings demonstrate that,
although anoxia decreases endothelial glutathione content, the endothelium
is able to utilize its remaining glutathione to protect against additional
oxidant stress because glutathione peroxidase and glutathione reductase
retain their activity.
