Over-expression of human phospholipase C-gamma 2 enhances platelet-derived growth factor-induced mobilization of intracellular Ca2+ and the release of arachidonic acid and prostaglandins in NIH 3T3 fibroblasts.
Over-expression of human phospholipase C-gamma 2 in murine NIH 3T3 fibroblasts has been shown to result in an increased platelet-derived growth factor-mediated formation of inositol phosphates. Here we show that phospholipase C-gamma 2 over-expression is associated with an increased platelet-derived growth factor-mediated release of arachidonic acid, prostaglandin E2, 6-keto prostaglandin F1 alpha and prostaglandin F2 alpha. The phorbol ester, calcium ionophore- and fluoride-induced release of arachidonate and its metabolites is not affected by phospholipase C-gamma 2 over-expression. Over-expression of phospholipase C-gamma 2 is also associated with an enhancement of platelet-derived growth factor-induced change in intracellular Ca2+. These results demonstrate that stimulation of recombinant human phospholipase C-gamma 2 induces a change in the intracellular Ca2+ concentration, a release of arachidonic acid and formation of prostaglandins in NIH 3T3 cells. In control cells platelet-derived growth factor-induced activation of arachidonic acid cascade is rate-limited by the endogenous phospholipase C.
Totzke
F
F
University of Freiburg, Institute of Molecular Cell Biology, Gödecke AG, Germany.
Hug
H
H
Fitzke
E
E
Marmé
D
D
Dieter
P
P
D016475:3T3 Cells; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D002851:Chromatography, High Pressure Liquid; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D002413:Cations, Divalent; D010982:Platelet-Derived Growth Factor; D011453:Prostaglandins; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D010738:Type C Phospholipases; D002118:Calcium