title: Bis(L-cysteinato)zincate(lI) as a coordination compound that induces metallothionein gene transcription without inducing cell-stress-related gene transcription.
abstract: 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.
authors.affiliation: Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan. tomoki@pharm.setsunan.ac.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Minako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Uno
authors.forename: Masakazu
authors.initials: M
authors.lastname: Isobe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naka
authors.forename: Shuji
authors.initials: S
authors.lastname: Yasuike
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
authors.forename: Masanobu
authors.initials: M
authors.lastname: Uchiyama
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D015032:Zinc / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; C583563:bis(cysteinato)zincate(lI); D008668:Metallothionein; D015032:Zinc; D003545:Cysteine