Zinc homeostasis and signaling in health and diseases

Fukada, Toshiyuki; Yamasaki, Satoshi; Nishida, Keigo; Murakami, Masaaki; Hirano, Toshio

doi:10.1007/s00775-011-0797-4

Cited by 530 publications

(442 citation statements)

References 155 publications

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“…Instead, it rapidly increases the expression of the ZIP8 importer located on the lysosomal membrane (79,80). However, this action also elevates the free Zn levels in the cytosol, which can trigger the production of inflammatory cytokines, resulting in T-cell proliferation (81,82). Despite occurring through different mechanisms, both bacterial and fungal infections result in increased free Zn within innate immune cells.…”

Section: Alterations In Host Cu and Zn Status In Response To Bacteriamentioning

confidence: 99%

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Djoko¹,

Ong²,

Walker

et al. 2015

Journal of Biological Chemistry

345

268

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Zinc (Zn) and copper (Cu) are essential for optimal innate immune function, and nutritional deficiency in either metal leads to increased susceptibility to bacterial infection. Recently, the decreased survival of bacterial pathogens with impaired Cu and/or Zn detoxification systems in phagocytes and animal models of infection has been reported. Consequently, a model has emerged in which the host utilizes Cu and/or Zn intoxication to reduce the intracellular survival of pathogens. This review describes and assesses the potential role for Cu and Zn intoxication in innate immune function and their direct bactericidal function.Six first row d-block metal ions, manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), and zinc (Zn), are essential micronutrients in living organisms. Investigations and discussions of the roles of these trace metals in biology often relate to their acquisition, storage, and incorporation into enzymes. However, conditions where these metal ions are present in excess or are found in the wrong location, resulting in toxicity, have also been described. Thus, there are also systems that sequester, export, and detoxify excess trace metal ions. Today, the concept of trace metal homeostasis, in which various cellular actions maintain the fine balance between nutrition and toxicity, is well developed.Recently, the concept of "nutritional immunity" has emerged in the context of host defense against pathogens. This envisages a role for mechanisms that protect the host from invading pathogens by restricting their ability to acquire key transition metal ions. One example involves lipocalin, which binds siderophores and thereby prevents Fe acquisition by bacterial pathogens (1). Another is calprotectin, which restricts acquisition of Zn or Mn (2). However, what if the host was able to harness the toxic properties of transition metal ions and use them as bactericides? This review explores the evidence for an antimicrobial role for Cu and Zn in the host defense against bacterial pathogens.

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Section: Alterations In Host Cu and Zn Status In Response To Bacteriamentioning

confidence: 99%

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Djoko¹,

Ong²,

Walker

et al. 2015

Journal of Biological Chemistry

345

268

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“…The analysis was conducted specifically on Zip (Zip1-Zip6, Zip8, Zip10, and Zip14) associated with the uptake of zinc into cells (17).…”

Section: Expression Analysis Of Zinc Transporters In the Skinmentioning

confidence: 99%

ZIP2 Protein, a Zinc Transporter, Is Associated with Keratinocyte Differentiation

Inoue

Hasegawa

Ban³

et al. 2014

Journal of Biological Chemistry

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Background: Few studies have investigated the ZIP proteins specifically expressed in keratinocytes. Results: ZIP2 is highly expressed in differentiating keratinocytes, and their differentiation is inhibited by ZIP2 siRNA. Conclusion: ZIP2 is essential for the differentiation of keratinocytes. Significance: Understanding the regulation of keratinocyte differentiation by zinc and its transporters is crucial for developing new therapies against skin disease.

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“…Evidence of altered zinc homeostasis in the etiology of diseases, including diabetes, Alzheimer's and cancer (Fukada et al 2011) highlights the importance of studying Zn 2C -regulated gene expression. A better understanding of the zinc-gastrin axis may aid in unraveling the role of zinc signaling in the EMT and in various pathological conditions.…”

Section: Cmentioning

confidence: 99%

Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter

Xiao

Kovac

Chang

et al. 2014

Journal of Molecular Endocrinology

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Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn 2C ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55G14-fold at 100 mM (P!0.05). . Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn 2C -dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial-mesenchymal transition (EMT), together with our observation that Zn 2C ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn 2C ions may induce an EMT, and that gastrin may be involved in the transition.

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Zinc homeostasis and signaling in health and diseases

Cited by 530 publications

References 155 publications

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

ZIP2 Protein, a Zinc Transporter, Is Associated with Keratinocyte Differentiation

Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter

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