Hydrogen peroxide activation of Ca(2+)-independent phospholipase A(2) in uterine stromal cells.
In rat uterine stromal cells (U(III) cells), an oxidative stress induced by H(2)O(2) caused a dose-dependent release of arachidonic acid (AA) that was independent of intracellular Ca(2+) concentration and was not inhibited by Ca(2+)-dependent phospholipase A(2) (cPLA(2)) inhibitors, nor by protein kinase C (PKC) inhibitors or by PKC down-regulation. H(2)O(2) treatment did not impair AA esterification but significantly increased Ca(2+)-independent PLA(2) (iPLA(2)) activity. Since iPLA(2) specific inhibitor bromoenollactone almost completely suppressed the release of AA induced by H(2)O(2), we conclude that iPLA(2) activity represents the major mechanism by which H(2)O(2) increases the availability of non-esterified AA in U(III) cells. Moreover, PKC inhibitors sphingosine and calphostin C markedly potentiated the release of AA trigger by H(2)O(2), suggesting a regulatory mechanism of iPLA(2) by PKC that remains to be clarified.
Birbes
H
H
Biochimie & Pharmacologie, INSERM U352, INSA-Lyon, Bât. 406, Villeurbanne Cedex, 69621, France.
Gothié
E
E
Pageaux
J F
JF
Lagarde
M
M
Laugier
C
C
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004951:Esterification / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism* / Q000502:physiology; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014599:Uterus / Q000166:cytology / Q000187:drug effects*
D005227:Fatty Acids; D016877:Oxidants; D010743:Phospholipids; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D010741:Phospholipases A; D002118:Calcium