Bis(l-cysteinato)zincate(lI) as a coordination compound that induces metallothionein gene transcription without inducing cell-stress-related gene transcription

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. 65Zn incorporation following treatment with 65Zn-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 ZnSO4 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.

Zinc coordination compounds may serve as specific zinc protein functional modulators. We found that, from a library of 30 zinc coordination compounds, bis(l-cysteinato)zincate(lI), 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.Figure optionsDownload as PowerPoint slideHighlights
► Zinc coordination compounds may serve as specific zinc protein functional modulators.
► To find the compounds, we constructed a library of 30 zinc complexes.
► Metallothionein (MT) transcription is mediated by the transcription factor MTF-1.
► Bis(l-cysteinato)zincate(lI) functioned as a MT inducer.
► Bis(l-cysteinato)zincate(II) might effectively transfer zinc to MTF-1.