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- Title
Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?
- Authors
Egefjord, Lærke; Jensen, Jens Ledet; Bang-Berthelsen, Claus Heiner; Petersen, Andreas Brønden; Smidt, Kamille; Schmitz, Ole; Karlsen, Allan Ertman; Pociot, Flemming; himienti, Fabrice; Rungby, Jørgen; Magnusson, Nils E.
- Abstract
Background: β-cells are extremely rich in zinc and zinc homeostasis is regulated by zinc transporter proteins. β-cells are sensitive to cytokines, interleukin-1β (IL-1β) has been associated with β-cell dysfunction and -death in both type 1 and type 2 diabetes. This study explores the regulation of zinc transporters following cytokine exposure. Methods: The effects of cytokines IL-1β, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on zinc transporter gene expression were measured in INS-1-cells and rat pancreatic islets. Being the more sensitive transporter, we further explored ZnT8 (Slc30A8): the effect of ZnT8 over expression on cytokine induced apoptosis was investigated as well as expression of the insulin gene and two apoptosis associated genes, BAX and BCL2. Results: Our results showed a dynamic response of genes responsible for β-cell zinc homeostasis to cytokines: IL-1β down regulated a number of zinc-transporters, most strikingly ZnT8 in both islets and INS-1 cells. The effect was even more pronounced when mixing the cytokines. TNF-α had little effect on zinc transporter expression. IFN-γ down regulated a number of zinc transporters. Insulin expression was down regulated by all cytokines. ZnT8 over expressing cells were more sensitive to IL-1β induced apoptosis whereas no differences were observed with IFN-γ, TNF-α, or a mixture of cytokines. Conclusion: The zinc transporting system in β-cells is influenced by the exposure to cytokines. Particularly ZnT8, which has been associated with the development of diabetes, seems to be cytokine sensitive.
- Subjects
ZINC; GENE expression; CYTOKINES; PANCREATIC beta cells; APOPTOSIS; INTERLEUKINS; DIABETES; TYPE 2 diabetes
- Publication
BMC Endocrine Disorders, 2009, Vol 9, p1
- ISSN
1472-6823
- Publication type
Article
- DOI
10.1186/1472-6823-9-7