Zinc and its Specific Transporters as Potential Targets in Airway Disease

Murgia, Chiara; Lang, Carol J.; Truong-Tran, Ai Q.; Grosser, Dion; Jayaram, Lata; Ruffin, Richard E.; Perozzi, Giuditta; Zalewski, Peter D.

doi:10.2174/138945006776818683

Cited by 39 publications

(36 citation statements)

References 183 publications

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“…Bioavailability of Zn is controlled by Zn homoeostatic mechanisms that involve Zn uptake, efflux and Zn distribution in cells (Murgia et al 2006). When comparing dose-response effects of zinc concentrations in medium and intracellular zinc (Fig.…”

Section: Discussionmentioning

confidence: 99%

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

et al. 2011

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Zinc (Zn) is an essential component of Zn-finger proteins and acts as a cofactor for enzymes required for cellular metabolism and in the maintenance of DNA integrity. The study investigated the genotoxic and cytotoxic effects of Zn deficiency or excess in a primary human oral keratinocyte cell line and determined the optimal concentration of two Zn compounds (Zn Sulphate (ZnSO 4 ) and Zn Carnosine (ZnC)) to minimise DNA damage. Zn-deficient medium (0 lM) was produced using Chelex treatment, and the two Zn compounds ZnSO 4 and ZnC were tested at concentrations of 0.0, 0.4, 4.0, 16.0, 32.0 and 100.0 lM. Cell viability was decreased in Zndepleted cells (0 lM) as well as at 32 lM and 100 lM for both Zn compounds (P \ 0.0001) as measured via the MTT assay. DNA strand breaks, as measured by the comet assay, were found to be increased in Zn-depleted cells compared with the other treatment groups (P \ 0.05). The Cytokinesis Block Micronucleus Cytome assay showed a significant increase in the frequency of both apoptotic and necrotic cells under Zn-deficient conditions (P \ 0.05). Furthermore, elevated frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) were observed at 0 and 0.4 lM Zn, whereas these biomarkers were minimised for both Zn compounds at 4 and 16 lM Zn (P \ 0.05), suggesting these concentrations are optimal to maintain genome stability. Expression of PARP, p53 and OGG1 measured by western blotting was increased in Zn-depleted cells indicating that DNA repair mechanisms are activated. These results suggest that maintaining Zn concentrations within the range of 4-16 lM is essential for DNA damage prevention in cultured human oral keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

et al. 2011

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“…Within the human body there are approximately 2 to 3 g of zinc distributed in a nonuniform pattern in cells and extracellular fluids (13). The small intestine absorbs approximately 3 to 4 mg/day, and therefore current recommended daily allowances range from 5 mg/day for infants to 16 to 19 mg/day for lactating women (13). Zinc is stored and/or used in two relatively distinct pools; the first is the fixed pool of zinc that is bound to metalloproteins.…”

Section: Discussionmentioning

confidence: 99%

“…approximately 80 to 90% of total body zinc and turns over very slowly (13,15). The second pool is the labile pool, which includes free or loosely bound zinc that is available for exchange among cells and organelles (13,15).…”

Section: Discussionmentioning

confidence: 99%

“…Zinc is an abundant and critical micronutrient; two families of transporters as well as storage/carrier proteins tightly regulate its tissue, cellular, and organellar distribution (13). It is a co-factor for at least 300 known enzymes including several key antioxidants, and is vital for the function of thousands of transcription factors; as such it is critically involved in cell growth, differentiation, and function (14,15).…”

Section: Abstract: Gm-csf; Phagocytosis; Tight Junctions; Zinc Transpmentioning

confidence: 99%

“…Further, although alcohol abuse has long been associated with zinc deficiency, the mechanisms for and the potential impact of this zinc deficiency have not been systematically examined. Based on the evolving understanding of the critical role of zinc in maintaining normal epithelial and immune function (13,16,17), alcohol-induced zinc deficiency within the alveolar space would have severe consequences for lung health (16).…”

Section: Abstract: Gm-csf; Phagocytosis; Tight Junctions; Zinc Transpmentioning

confidence: 99%

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Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

Joshi¹,

Mehta²,

Jabber³

et al. 2009

Am J Respir Cell Mol Biol

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Chronic alcohol abuse impairs both alveolar epithelial and macrophage function, and renders individuals susceptible to acute lung injury, pneumonia, and other serious lung diseases. Zinc deficiency, which is known to impact both epithelial and immune cell functions, is also associated with alcohol abuse. In this study, chronic alcohol ingestion (6 wk) in rats altered expression of key zinc transporters and storage proteins in the small intestine and the lung, and decreased zinc levels in the alveolar compartment. Zinc supplementation of alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function, and these improvements were associated with salutary changes in tight junction protein expression and membrane localization. In parallel, dietary zinc supplementation increased intracellular zinc levels, GM-CSF receptor expression, and bacterial phagocytic capacity in the alveolar macrophages of alcoholfed rats. Together, these studies implicate zinc deficiency as a novel mechanism mediating alcohol-induced alveolar epithelial and macrophage dysfunction. Importantly, these findings argue that dietary supplementation can overcome alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage function, and therefore could be an effective treatment for the susceptible alcoholic lung phenotype.

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The effect of combined exposure of zinc and nickel on the development of zebrafish

Yang

Zhou

et al. 2021

J of Applied Toxicology

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Excessive accumulation of Zn2+ or Ni2+ can cause various problems to aquatic animals. In this study, the developmental toxicity induced by individual or combined exposure of Zn2+ and Ni2+ to zebrafish embryos and larvae were evaluated to better understand the interaction between Zn2+ and Ni2+. Both of individual and combined exposure of Zn2+ and Ni2+ could cause obvious developmental toxicity, which mainly occurred after hatching, at a concentration‐dependent manner. The calculated 168‐h LC50 were 2.79 mg/L for Zn2+ and 7.44 mg/L for Ni2+. The interaction of Zn2+ and Ni2+ based on mortality was found to be an antagonism. Various malformations, including tail curving, spinal curvature, pericardial edema, and yolk sac edema, were observed with significant effects on body length and heartbeat rates after exposure of Zn2+ and Ni2+. Meanwhile, some genes related to cardiovascular development and bone formation were mainly down‐regulated by the individual and combined exposure of Zn2+ and Ni2+. The individual exposure was more toxic than combined exposure because the interaction of Zn2+ and Ni2+ was determined to be an antagonism. The down‐regulation of genes related to cardiovascular development and bone formation may contribute to the observed malformation and decreases of body length and heartbeat rates.

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Zinc and its Specific Transporters as Potential Targets in Airway Disease

Cited by 39 publications

References 183 publications

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

The effect of combined exposure of zinc and nickel on the development of zebrafish

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