title: Interferonbeta-induced changes in metallothionein expression and subcellular distribution of zinc in HepG2 cells.
abstract: We evaluated the changes of metallothionein induction and cellular zinc distribution in HepG2 cells by interferonbeta treatment. Immunohistochemical staining of metallothionein was observed in the cytoplasm and nuclei of hepatocytes; which was observed predominantly in the cells treated with interferon and zinc compared to those with zinc alone, interferon alone or the no-treated control. The cellular zinc level was higher in order of the interferon- and zinc-treated cells, the zinc-alone-treated cells, and the interferon-alone-treated cells. Flow cytometry showed that S-phase population increased in interferon-alone-treated cells and interferon- and zinc-treated cells, but not in zinc-alone-treated ones. Cellular elemental distribution was analyzed using in-air micro-particle induced X-ray emission. In zinc-alone-treated sample, X-ray spectra showed good consistency between the enhanced cellular zinc distribution and the phosphorous map. Localizations of bromine followed by interferon treatment were found accompanying a spatial correlation with the phosphorous map. The samples treated with interferon and zinc showed the marked accumulation of zinc and bromine. Discrete bromine accumulation sites were clearly visible with a strong spatial correlation followed by zinc accumulation. These findings suggest that interferonbeta in combination with zinc predominantly induces metallothionein expression in HepG2 cells. In addition, interferonbeta may promote the translocation of metallothionein-bound zinc from cytoplasm to S-phase nuclei.
authors.affiliation: Gunma University Graduate School of Medicine, Faculty of Medicine, Course of Health Science, 3-39-15 Showa-machi, Maebashi 371-8514, Japan. mine@health.gunma-u.ac.jp
authors.forename: Takeaki
authors.initials: T
authors.lastname: Nagamine
authors.forename: Takahiki
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takada
authors.forename: Kyoumi
authors.initials: K
authors.lastname: Nakazato
authors.forename: Takuro
authors.initials: T
authors.lastname: Sakai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Oikawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Arakawa
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000494:pharmacology*; D008668:Metallothionein / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D016899:Interferon-beta; D008668:Metallothionein; D015032:Zinc