Functions of zinc in signaling, proliferation and differentiation of mammalian cells

Beyersmann, Detmar; Haase, Hajo

doi:10.1007/978-94-017-3728-9_8

Cited by 162 publications

(214 citation statements)

References 75 publications

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“…Zinc ions released intracellularly from the zinc/ thiolate clusters of MTs or secreted from specialized organelles are potent effectors of proteins and are considered zinc signals (47,48). The observed increase in labile zinc was unaltered after silencing MTs, suggesting that they are not the source of this zinc.…”

Section: Discussionmentioning

confidence: 99%

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

Arriaga

Greco

Mordoh

et al. 2014

Molecular Cancer Therapeutics

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Metallothioneins (MT) are a family of low molecular weight proteins that are silenced during colorectal cancer progression, mainly through epigenetic mechanisms, and this loss is associated with poor survival. In this article, we show that overexpression of the MT1G isoform sensitizes colorectal cell lines to the chemotherapeutic agents oxaliplatin (OXA) and 5-fluorouracil (5-FU), in part through enhancing p53 and repressing NF-kB activity. Despite being silenced, MTs can be reinduced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate. In fact, this induction contributes to the cytotoxicity of these agents, given that silencing of MTs by siRNAs reduces their growth-inhibitory activities. Zinc ions also potently enhance MT expression and are cytotoxic to cancer cells. We show for the first time that OXA and 5-FU induce higher levels of intracellular labile zinc, as measured using the fluorescent probe FLUOZIN-3, and that such zinc contributes to the activation of p53 and repression of NF-kB. Addition of zinc enhanced growth inhibition by OXA and 5-FU, and was also capable of resensitizing 5-FU-resistant cell lines to levels comparable with sensitive cell lines. This effect was MT independent because silencing MTs did not affect zinc cytotoxicity. In conclusion, we show that MT induction and zinc administration are novel strategies to sensitize colorectal cancer cells to presently utilized chemotherapeutic agents. Mol Cancer Ther; 13(5); 1369-81. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

Arriaga

Greco

Mordoh

et al. 2014

Molecular Cancer Therapeutics

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“…Metallothioneins (MTs) are essential to intracellular zinc homeostasis by sequestration of the metal and thereby controlling available free zinc (Sato et al, 1984;Beyersmann and Haase, 2001;Coyle et al, 2002). The cysteine sulfur ligands in the cluster structure of MTs can be oxidized and reduced with concomitant changes in bound zinc (Maret, 1994(Maret, , 1995Maret and Vallee, 1998;Maret et al, 1999).…”

Section: Zinc Participates In Gene Expression Controlmentioning

confidence: 99%

“…Very recently, MTF-2, an ortholog of MTF-1, was identified as another zinc-dependent transcription factor (Cousins et al, 2003). There appears to be a huge number of 'zinc-regulated' genes in all organisms and it remains to be determined how zinc availability in a cell controls target gene transcription directly or secondarily by indirect mechanisms (Beyersmann and Haase, 2001). …”

Section: Zinc Participates In Gene Expression Controlmentioning

confidence: 99%

Nutrient-gene interactions: a single nutrient and hundreds of target genes

Daniel¹,

Dieck²

2004

Biological Chemistry

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Based on the effects of a selective experimental zinc deficiency in a rodent model we explore the use of transcriptome profiling for assessing nutrient-gene interactions in the liver at the molecular and cellular levels. Zinc deficiency caused pleiotropic alterations in mRNA/protein levels of hundreds of genes. In the context of observed metabolic alterations in hepatic metabolism, possible mechanisms are discussed for how a low zinc status may be sensed and transmitted into changes in various metabolic pathways. However, it also becomes obvious that analysis of such complex nutrient-gene interactions beyond the descriptional level is a real challenge for systems biology.

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“…Zinc is not redox-active, but nevertheless toxic when in excess (Beyersmann and Haase, 2001). Acute zinc toxicity is rare but has been reported (Duncan et al, 1992;Whittaker, 1998;Prasad et al, 1999).…”

mentioning

confidence: 99%

“…Acute zinc toxicity is rare but has been reported (Duncan et al, 1992;Whittaker, 1998;Prasad et al, 1999). If the extracellular concentration of zinc exceeds the capacity of zinc homeostasis mechanisms, it becomes cytotoxic and an excess of free intracellular zinc can trigger apoptosis (Choi et al, 1988;Duncan et al, 1992;Kim et al, 1999;Beyersmann and Haase, 2001;Wilhelm et al, 2001;Beyersmann, 2002;Walther et al, 2003). Zinc transport in Drosophila, as in vertebrates, is mediated by two families of solute linked carrier proteins: zinc importers (ZIPs), which function in the uptake of zinc to the cytoplasm, and zinc exporters (ZnTs), which reduce cytoplasmic zinc concentrations by promoting zinc efflux (Liuzzi and Cousins, 2004;Yepiskoposyan et al, 2006).…”

mentioning

confidence: 99%

Zinc supplement greatly improves the condition of parkin mutant Drosophila

Saini

Schaffner

2010

Biological Chemistry

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Parkinson's disease (PD) is a progressive neurodegenerative disorder in which oxidative stress is implicated as a major causative factor. Mutations in the gene encoding Parkin, a ubiquitin ligase, are responsible for a familial form of PD. In a Drosophila disease model lacking Parkin (park 25 null mutant), we tested the effect of zinc supplementation. Zinc is an essential trace metal and a component of many enzymes and transcriptional regulators. Unlike copper and iron, zinc is not redox-active and under most conditions serves as an antioxidant. We find that the condition of parkin mutants raised on zinc-supplemented food is greatly improved. At zinc concentrations where controls begin to show adverse effects as a result of the metal supplement, parkin mutants perform best, as manifested in a higher frequency of reaching adulthood, extended lifespan and improved motoric abilities.

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Functions of zinc in signaling, proliferation and differentiation of mammalian cells

Cited by 162 publications

References 75 publications

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

Nutrient-gene interactions: a single nutrient and hundreds of target genes

Zinc supplement greatly improves the condition of parkin mutant Drosophila

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