Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?
Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?
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DOI：
10.1186/1472-6823-9-7
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发表时间：
2009-02-25
影响因子：
2.7
通讯作者：
Magnusson NE
中科院分区：
文献类型：
--
作者：
Egefjord L;Jensen JL;Bang-Berthelsen CH;Petersen AB;Smidt K;Schmitz O;Karlsen AE;Pociot F;Chimienti F;Rungby J;Magnusson NE
β细胞富含锌，锌的体内平衡由锌转运蛋白调节。β-细胞对细胞因子敏感，白细胞介素-1β (IL-1β)与1型和2型糖尿病中β-细胞功能障碍和死亡有关。本研究探讨细胞因子暴露后锌转运蛋白的调控。测定细胞因子IL-1β、干扰素-γ (IFN-γ)和肿瘤坏死因子-α (TNF-α)对ins -1细胞和大鼠胰岛锌转运蛋白基因表达的影响。作为更敏感的转运体，我们进一步探索了ZnT8 (Slc30A8)：我们研究了ZnT8过表达对细胞因子诱导的细胞凋亡的影响，以及胰岛素基因和两个凋亡相关基因BAX和BCL2的表达。我们的研究结果显示了负责β细胞锌稳态的基因对细胞因子的动态响应：IL-1β下调了许多锌转运蛋白，在胰岛和INS-1细胞中最显著的是ZnT8。当混合细胞因子时，效果更加明显。TNF-α对锌转运蛋白表达影响较小。IFN-γ下调了许多锌转运蛋白。所有细胞因子均下调胰岛素表达。ZnT8过表达的细胞对IL-1β诱导的细胞凋亡更敏感，而IFN-γ、TNF-α或多种细胞因子的细胞凋亡无差异。β细胞中的锌转运系统受细胞因子的影响。尤其是与糖尿病相关的ZnT8，似乎对细胞因子很敏感。
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. 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. 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. 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.
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影响因子：
5.8
作者：
Andersen, HU;Mauricio, D;Nerup, J
通讯作者：
Nerup, J
DOI：
10.1007/bf02827241
发表时间：
1997-04-01
期刊：
INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH
影响因子：
--
作者：
Cavallo, MG;Monetini, L;Pozzilli, P
通讯作者：
Pozzilli, P
影响因子：
5.8
作者：
Chimienti, F;Seve, M;Favier, A
通讯作者：
Favier, A
影响因子：
7.7
作者：
Chandra, J;Yang, SN;Orrenius, S
通讯作者：
Orrenius, S
影响因子：
4
作者：
Chimienti, Fabrice;Devergnas, Severine;Seve, Michel
通讯作者：
Seve, Michel