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Signal transduction by bFGF, but not TGFβ1, involves arachidonic acid metabolism in endothelial cells
Author(s) -
Fafeur VéRonique,
Jiang Zhi Ping,
Böhlen Peter
Publication year - 1991
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041490214
Subject(s) - arachidonic acid , basic fibroblast growth factor , phospholipase a2 , inositol , biology , growth factor , biochemistry , eicosanoid , metabolism , endocrinology , medicine , chemistry , receptor , enzyme
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 (TGFβ1), with their specific receptors on bovine endothelial cells. At mitogenic concentrations, bFGF stimulated the rapid release of arachidonic acid and its metabolites from ( 3 H)‐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‐ 3 H)‐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. TGFβ1, which inhibits basal and bFGF‐induced endothelial cell growth, had no effect on arachidonic acid matabolism and inositol phosphate formation and did not prevent bFGF‐induced arachidonic acid metabolism. These results suggest that the inhibitory action of TGFβ1 on endothelial cell growth occurs through different mechanisms.