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Heparan sulfate chains potentiate cadmium cytotoxicity in cultured vascular endothelial cells

  • Inorganic Compounds
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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.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (B) #24390034 from the Japan Society for the Promotion of Science (to T. K.).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, 192-0392, Japan

    Yasuyuki Fujiwara

  2. Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, 274-8510, Japan

    Chika Yamamoto

  3. Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan

    Eiko Yoshida & Toshiyuki Kaji

  4. Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan

    Yoshito Kumagai

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  1. Yasuyuki Fujiwara
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  2. Chika Yamamoto
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  3. Eiko Yoshida
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  4. Yoshito Kumagai
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Correspondence to Toshiyuki Kaji.

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Fujiwara, Y., Yamamoto, C., Yoshida, E. et al. Heparan sulfate chains potentiate cadmium cytotoxicity in cultured vascular endothelial cells. Arch Toxicol 90, 259–267 (2016). https://doi.org/10.1007/s00204-014-1420-6

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  • DOI: https://doi.org/10.1007/s00204-014-1420-6

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