Signal transduction by bFGF, but not TGF beta 1, involves arachidonic acid metabolism in endothelial cells.
We investigated the stimulation of early cellular events resulting from the interaction of the growth factor basic FGF (bFGF) and of the growth inhibitor transforming growth factor beta-type 1 (TGF beta 1), with their specific receptors on bovine endothelial cells. At mitogenic concentrations, bFGF stimulated the rapid release of arachidonic acid and its metabolites from (3H)-arachidonic acid labeled cells. When arachidonic acid metabolism was stimulated by addition of the calcium ionophore A23187, the effect of bFGF was amplified. Nordihydroguaïaretic acid, an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism, decreased the mitogenic effect of bFGF, whereas indomethacin, an inhibitor of the cyclooxygenase pathway, was ineffective. These findings suggest that metabolism of arachidonic acid to lipoxygenase products may be necessary for the mitogenic effect of bFGF. Basic FGF did not stimulate the production of inositol phosphates from cells labelled with myo-(2-3H)-inositol nor did it induce calcium mobilization, as measured by fura-2 fluorescence, indicating that bFGF does not activate phosphoinositide-specific phospholipase C in endothelial cells, but rather, that bFGF-induced arachidonic acid metabolism is mediated by another phospholipase. TGF beta 1, which inhibits basal and bFGF-induced endothelial cell growth, had no effect on arachidonic acid metabolism and inositol phosphate formation and did not prevent bFGF-induced arachidonic acid metabolism. These results suggest that the inhibitory action of TGF beta 1 on endothelial cell growth occurs through different mechanisms.
Fafeur
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Medical Research Division, American Cyanamid, Pearl River, New York 10965.
Jiang
Z P
ZP
Böhlen
P
P
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D009637:Masoprocol / Q000494:pharmacology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D002712:Chlorides; D007295:Inositol Phosphates; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D016718:Arachidonic Acid; D009637:Masoprocol; D008094:Lithium; D018021:Lithium Chloride; D001920:Bradykinin; D002118:Calcium; D007213:Indomethacin