The participation of hydroperoxides and oxygen radicals in the control of prostaglandin synthesis.

Our results demonstrate that the organic hydroperoxide t-butyl-hydroperoxide (TBHP) influences the synthesis of prostaglandins in the human embryo lung fibroblast. TBHP inhibits or stimulates prostaglandin synthesis as a function of its concentration. Regardless of the concentration employed in these experiments however, TBHP stimulated the release of arachidonate from lipid stores. When the arachidonate release step in prostaglandin (PG) synthesis was bypassed by the addition of free arachidonate to the cell cultures, t-butyl hydroperoxide further stimulated PG synthesis, indicating that the hydroperoxide activates arachidonate conversion to prostaglandins. 4-Hydroxy-2,2,6,6-tetramethylpiperidinoxy radical, a scavenger of oxygen radicals, when added to cell cultures alone had no measurable effect on either arachidonate release or prostaglandin synthesis. When 4-hydroxy-2,2,6,6-tetramethylpiperidinoxy radical was administered to cell cultures in combination with t-butyl hydroperoxide, it increased prostaglandin synthesis while inhibiting arachidonate release by the hydroperoxide. The participation of hydroperoxides and trappers of oxygen radicals in the regulation of PG synthesis is not unique to lung fibroblasts. Endothelial cells from the vasculature as well as fibroblasts from the cornea also appear to be affected by these compounds with respect to prostaglandin synthesis.