Mammalian Zinc Transport, Trafficking, and Signals

Cousins, Robert J.; Liuzzi, Juan P.; Lichten, Louis A.

doi:10.1074/jbc.r600011200

Cited by 611 publications

(488 citation statements)

References 64 publications

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“…19 In zinc deficient cells, Zip-transporters responsible for the movement of zinc into the cytosol are upregulated, while transporters of the ZnT-type needed for the reverse transport are downregulated. 8,[20][21][22][23][24] In our hands zinc is removed from the culture medium by CHELEX with over 90% efficiency. The remainder might still be sufficient for the cells to maintain free zinc, despite a state of general zinc deficiency.…”

Section: Discussionmentioning

confidence: 99%

Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes

et al. 2014

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Zinc deficiency has a fundamental influence on the immune defense, with multiple effects on different immune cells, resulting in a major impairment of human health. Monocytes and macrophages are among the immune cells that are most fundamentally affected by zinc, but the impact of zinc on these cells is still far from being completely understood. Therefore, this study investigates the influence of zinc deficiency on monocytes of healthy human donors. Peripheral blood mononuclear cells, which include monocytes, were cultured under zinc deficient conditions for 3 days. This was achieved by two different methods:by application of the membrane permeable chelator N,N,N 0 ,N 0 -tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) or by removal of zinc from the culture medium using a CHELEX 100 resin. Subsequently, monocyte functions were analyzed in response to Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Zinc depletion had differential effects. On the one hand, elimination of bacterial pathogens by phagocytosis and oxidative burst was elevated. On the other hand, the production of the inflammatory cytokines tumor necrosis factor (TNF)-a and interleukin (IL)-6 was reduced. This suggests that monocytes shift from intercellular communication to basic innate defensive functions in response to zinc deficiency.These results were obtained regardless of the method by which zinc deficiency was achieved. However, CHELEX-treated medium strongly augmented cytokine production, independently from its capability for zinc removal. This side-effect severely limits the use of CHELEX for investigating the effects of zinc deficiency on innate immunity.

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Section: Discussionmentioning

confidence: 99%

Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes

et al. 2014

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“…Cyclo(His-Pro) has a chelating effect on zinc and assists in zinc transport through an intestinal Cyclo(His-Pro) transporting mechanism independent of the normal elemental zinc transport system [73]. The normal elemental zinc absorption mechanism is a facilitated diffusion transport process, via the zinc transporter (ZnT) proteins mediating zinc efflux and influx into intracellular vesicles [74]. These proteins contain a variable number of histidine, similar to Cyclo(His-Pro).…”

Section: Clinical Impact Of Insulin Degrading Enzyme (Ide) On Alzheimmentioning

confidence: 99%

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

et al. 2017

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BackgroundAssociation of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice.Scope of reviewMetabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues. Mechanistic effect of insulin degrading enzyme (IDE) in decreasing blood glucose and brain Aβ levels will be elucidated. Cyclo-Z effects on these biochemical parameters will be discussed.Major conclusionStimulation of IDE synthesis is effective for the clinical treatment of metabolic diseases including AD and T2D.General significanceCyclo-Z might be the effective treatment of AD and T2D by stimulating IDE synthesis.

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“…Zinc homeostasis is mostly regulated by zinc transporters (Eide 2006). Known eukaryotic zinc transporters are largely classified into two families, the ZRT/IRT-like Protein (ZIP) and Cation Diffusion Facilitator (CDF) families, which are designated as ''SLC39'', and ''SLC30'', respectively (Cousins et al 2006;Kambe et al 2004). ZIP members facilitate zinc influx into the cytosol, while CDF members facilitate its efflux from the cytosol.…”

Section: Introductionmentioning

confidence: 99%

Restraint stress up-regulates expression of zinc transporter Zip14 mRNA in mouse liver

et al. 2008

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The zinc concentration in the liver was significantly higher in mice at 12 h after the onset of restraint stress than that without stress. The IL-6 protein level in the serum was transiently elevated at 3 h after the onset of restraint stress, and the IL-6-responsive zinc transporter Zip14 mRNA in the liver was expressed markedly at 6 h. These results suggest that Zip14 plays a major role in the mechanism responsible for accumulation of zinc in the liver under restraint stress.

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Mammalian Zinc Transport, Trafficking, and Signals

Cited by 611 publications

References 64 publications

Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes

Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

Restraint stress up-regulates expression of zinc transporter Zip14 mRNA in mouse liver

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