title: Zinc diethyldithiocarbamate as an inducer of metallothionein in cultured vascular endothelial cells.
abstract: Vascular endothelial cells are in direct contact with blood. Inorganic zinc is thought to be incapable of inducing metallothionein, which protects cells from heavy metal toxicity and oxidative stress, in vascular endothelial cells. Here, we aimed to further characterize the induction of metallothionein in vascular endothelial cells. Our results confirmed that inorganic zinc could not induce metallothionein in vascular endothelial cells. Moreover, ZnSO4 could not activate both the metal response element (MRE) transcription factor 1 (MTF-1)/MRE and Nrf2/antioxidant response element (ARE) pathways and was incapable of inducing metallothionein. In addition, bis(L-cysteinato)zincate(II), a zinc complex that activates the MTF-1/MRE pathway, increased MRE promoter activity but failed to induce metallothionein, suggesting that vascular endothelial metallothionein was not induced only by activation of the MTF-1/MRE pathway. Further analysis of a library of zinc complexes showed that zinc(II) bis(diethyldithiocarbamate) activated the MTF-1/MRE pathway but not the Nrf2/ARE pathway, increased MT-1A, MT-1E, and MT-2A mRNA levels, and induced metallothionein proteins. These data indicated that zinc complexes may be excellent tools to analyze metallothionein induction in vascular endothelial cells.
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fujie
authors.forename: Yukino
authors.initials: Y
authors.lastname: Segawa
authors.forename: Akane
authors.initials: A
authors.lastname: Uehara
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.forename: Eiko
authors.initials: E
authors.lastname: Yoshida
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Masanobu
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism* / Q000502:physiology; D019216:Metals, Heavy / Q000633:toxicity; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D014157:Transcription Factors / Q000378:metabolism; D019287:Zinc Sulfate / Q000494:pharmacology; D000097809:Transcription Factor MTF-1
chemical_list: D004268:DNA-Binding Proteins; D004050:Ditiocarb; D008668:Metallothionein; D019216:Metals, Heavy; D051267:NF-E2-Related Factor 2; D014157:Transcription Factors; D019287:Zinc Sulfate; D000097809:Transcription Factor MTF-1; C495635:NFE2L2 protein, human