Signal transduction by bFGF, but not TGFβ1, involves arachidonic acid metabolism in endothelial cells

Abstract

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.

Arachidonic Acid–Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis

“…AA, preferentially through its metabolites, plays a key role in different phases of the angiogenic process, including endothelial cell proliferation (38)(39)(40). We previously showed that AA promotes cell proliferation in bovine aortic endothelial cells.…”

An Essential Role of the Jak-2/STAT-3/Cytosolic Phospholipase A2 Axis in Platelet-derived Growth Factor BB-induced Vascular Smooth Muscle Cell Motility

“…Arachidonic acid and its metabolites are involved in the regulation of a variety of physiological processes including vascular tone (23,24). In addition, these lipid molecules have been reported to mediate intracellular signaling events in response to a number of stimulants (25)(26)(27)(28)(29)(30). A large body of data also suggests that arachidonic acid and its metabolites play an important role in cell survival and proliferation (31)(32)(33)(34)(35).…”

5(S)-Hydroxyeicosatetraenoic Acid Stimulates DNA Synthesis in Human Microvascular Endothelial Cells via Activation of Jak/STAT and Phosphatidylinositol 3-Kinase/Akt Signaling, Leading to Induction of Expression of Basic Fibroblast Growth Factor 2

“…Arachidonic acid and its metabolites, known as eicosanoids, are involved in the regulation of a variety of biological processes including vascular tone (5,6). In addition, these lipid molecules have been reported to mediate intracellular signaling events in response to a number of stimuli (7)(8)(9)(10)(11)(12). A large body of pharmacological data suggests that arachidonic acid and its eicosanoid metabolites stimulate mitogenesis in various cell types, including cancer cells (13)(14)(15)(16)(17)(18)(19)(20).…”