title: Basic fibroblast growth factor-induced glycosaminoglycan production in cultured vascular endothelial cells results from enhanced protein synthesis mediated by the lipoxygenase pathway.
abstract: 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.
authors.affiliation: Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaji
authors.forename: A
authors.initials: A
authors.lastname: Miyamoto
authors.forename: C
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: S
authors.initials: S
authors.lastname: Miyajima
authors.forename: F
authors.initials: F
authors.lastname: Koizumi
mesh_terms: 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
chemical_list: D006025:Glycosaminoglycans; D016859:Lipoxygenase Inhibitors; D013431:Sulfates; D016222:Fibroblast Growth Factor 2; D009637:Masoprocol; D008084:Lipoxygenase; D007213:Indomethacin