Hydrogen peroxide activation of Ca2+-independent phospholipase A(2) in uterine stromal cells

In rat uterine stromal cells (U-III cells), an oxidative stress induced by H2O2 caused a dose-dependent release of arachidonic acid (AA) that was inde pendent of intracellular Ca2+ concentration and was not inhibited by Ca2+-d ependent phospholipase A(2) (cPLA(2)) inhibitors, nor by protein kinase C ( PKC) inhibitors or by PKC down-regulation. H2O2 treatment did not impair AA esterification but significantly increased Ca2+-independent PLA(2) (iPLA(2 )) activity. Since iPLA(2) specific inhibitor bromoenollactone almost compl etely suppressed the release of AA induced by H2O2, we conclude that iPLA(2 ) activity represents the major mechanism by which H2O2 increases the avail ability of nonesterified AA in U-III cells. Moreover, PKC inhibitors sphing osine and calphostin C markedly potentiated the release of AA trigger by H2 O2, suggesting a regulatory mechanism of iPLA(2) by PKC that remains to be clarified. (C) 2000 Academic Press.