Role of intracellular calcium in the regulation of phospholipase A2 in fMet-Leu-Phe-challenged human polymorph neutrophils.
In the present study, we have shown that the protein kinase C (PKC) inhibition by staurosporine augmented fMet-Leu-Phe-(FMLP)-induced arachidonic acid (AA) release in human polymorph neutrophils (PMN). This effect is in contradiction to a recently reported mechanism that besides Ca2+, the phosphorylation of cytosolic phospholipase A2 (cPLA2) is essential for the enzyme activation. In addition, we found that staurosporine elevated the basal concentration of intracellular Ca2+, although initial Ca2+ release was not affected. Since thapsigargin, a blocker of endogenous Ca2+ ATPase, also increased AA release dose-dependently, we believe that the elevation of intracellular Ca2+ is the most essential step and not the phosphorylation of enzyme for the activation of cPLA2.
Nigam
S
S
Department of Gynecology, University Medical Center Benjamin Franklin (Steglitz), Free University Berlin, Germany.
Eskafi
S
S
Garlichs
C
C
Firth
S
S
Zhang
H
H
D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013050:Spectrometry, Fluorescence
D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042205:methionyl-leucyl-phenylalanine; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium