Basic fibroblast growth factor-induced glycosaminoglycan production in cultured vascular endothelial cells results from enhanced protein synthesis mediated by the lipoxygenase pathway.
To investigate the intracellular regulation of glycosaminoglycan (GAG) production induced by basic fibroblast growth factor (bFGF), bovine aortic endothelial cells were cultured with recombinant human bFGF in the presence of [3H]glucosamine or [35S]sulfate. It was shown that bFGF-induced incorporation of the radioactive precursors into GAGs was diminished by lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) and esculetin, but not by a cyclooxygenase inhibitor indomethacin. A protein synthesis inhibitor cycloheximide also diminished the enhancement of the [3H]glucosamine incorporation by bFGF. On the other hand, the incorporation of [14C]leucine into the acid-insoluble fraction was strongly inhibited by NDGA but not by indomethacin in the presence or absence of bFGF. It was also shown that bFGF significantly increased the incorporation of [14C]xylose into GAGs. The present data suggested that bFGF may increase the number of GAG chains as a result of enhanced protein synthesis including xylosyl transferase through the lipoxygenase pathway of arachidonic acid metabolism in vascular endothelial cell layer.
Kaji
T
T
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Miyamoto
A
A
Yamamoto
C
C
Fujiwara
Y
Y
Miyajima
S
S
Koizumi
F
F
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism
D006025:Glycosaminoglycans; D016859:Lipoxygenase Inhibitors; D013431:Sulfates; D016222:Fibroblast Growth Factor 2; D009637:Masoprocol; D008084:Lipoxygenase; D007213:Indomethacin