title: Heparan sulfate chains potentiate cadmium cytotoxicity in cultured vascular endothelial cells.
abstract: The monolayer of vascular endothelial cells, which is rich in heparan sulfate chains, is an important target of cadmium cytotoxicity. To investigate the effects of heparan sulfate chains on cadmium cytotoxicity, bovine aortic endothelial cells were cultured in the presence of cadmium, with or without exogenous heparan sulfate. The following results were obtained: (1) Heparan sulfate chains potentiated cadmium cytotoxicity. (2) Such a potentiation did not occur in bovine aortic smooth muscle cells. (3) Heparin chains as well as heparan sulfate chains potentiated cadmium cytotoxicity, while other glycosaminoglycan chains failed to exhibit such an activity. (4) The disaccharide units of heparan sulfate chains did not potentiate cadmium cytotoxicity in the endothelial cells. (5) Heparan sulfate chains did not potentiate mercury and arsenite cytotoxicity. (6) Fibroblast growth factor-2 (FGF-2) also potentiated cadmium cytotoxicity in the endothelial cells. (7) Heparan sulfate chains significantly increased intracellular cadmium accumulation by inducing the expression of metallothionein. Taken together, these results suggest that heparan sulfate chains activate FGF-2, which in turn elevates the expression and/or activity of metal transporter(s) that facilitate cadmium influx from the extracellular space into the cytoplasm.
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, 192-0392, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, 274-8510, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Yoshida
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan. t-kaji@rs.noda.tus.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2; D006025:Glycosaminoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism* / Q000494:pharmacology; D008668:Metallothionein / Q000378:metabolism
chemical_list: D002104:Cadmium; D016222:Fibroblast Growth Factor 2; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008668:Metallothionein
keywords: Cadmium; Cytotoxicity; Endothelial cell; Heparan sulfate