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Impairment of cultured cell proliferation and metallothionein expression by metal chelator NNN’ N’-tetrakis-(2-pyridylmethyl) ethylene diamine

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Abstract

Metallothioneins (MT) are a family of intracellular, cysteine-rich, zinc-binding proteins. Their expression is constitutive but can also be induced at the transcriptional level by various stimuli. In this study, we exposed HaCaT human keratinocytes to excess zinc (ZnCl2) or to zinc deprivation by the diffusible chelator NNN’N’-tetrakis(2-pyridylmethyl) ethylene diamine (TPEN), and to ultraviolet B (UVB) irradiation. We examined both cell proliferation and MT expression. Cell proliferation was maximally stimulated by 100 ΜM Zn2+ supply and was markedly inhibited by zinc deprivation or UVB irradiation. Zinc and UVB irradiation both increased MTI and/or MTII as detected by immunocytochemistry and enhanced the baseline level of MT-IIA mRNA, whereas TPEN treatment inhibited MT basal expression. Zinc partially prevented the concentration-dependent, UVB-induced decrease in cell proliferation. On the other hand, TPEN partially prevented the UVB-induced increase in MTIIA mRNA. These results suggest that zinc is involved in defense mechanisms of skin keratinocytes and in their stress-induced response.

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Authors and Affiliations

  1. Groupe de Recherche sur les Pathologies Oxydatives, CHU Albert Michallon, BP 217 X, 38043, Grenoble Cedex, France

    Marie-Odile Parat, Marie-Jeanne Richard, Alain Favier & Jean-Claude Béani

  2. Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France

    Catherine Meplan

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  1. Marie-Odile Parat
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Parat, MO., Richard, MJ., Meplan, C. et al. Impairment of cultured cell proliferation and metallothionein expression by metal chelator NNN’ N’-tetrakis-(2-pyridylmethyl) ethylene diamine. Biol Trace Elem Res 70, 51–68 (1999). https://doi.org/10.1007/BF02783849

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