Zinc is an essential micronutrient, deficiency of which results in growth retardation, immunodeficiency, and neurological diseases such as dysgeusia. Several zinc coordination compounds are used for zinc supplementation; however, supplemented zinc ions have no specificity and interact with various groups of molecules. Here, we found that, from a library of 30 zinc coordination compounds, bis(L-cysteinato)zincate(II), designated Z01, functioned as a metallothionein (MT) inducer. Z01 induced MT expression mediated by the transcription factor MTF-1, without inducing cell-stress-related heme oxygenase-1 gene expression at specific concentration. The zinc ion was necessary for the MT induction. (65)Zn incorporation following treatment with (65)Zn-labeled Z01 suggested that Z01 did not act as zinc ionophore despite its hydrophilicity. Electrophoretic mobility shift assays revealed that Z01 facilitates MTF-1-MRE complex formation, and, by inference, transfer of zinc from Z01 to MTF-1. Phosphorylated ERK levels were increased by ZnSO(4) treatment but not by Z01. Although our data do not definitely prove that Z01 is an MTF-1-specific activator, our observations suggest that zinc coordination compounds can regulate zinc distribution and act as zinc donors for specific molecules.
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