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Nancy F. Krebs - One of the best experts on this subject based on the ideXlab platform.
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Major variables of Zinc Homeostasis in Chinese toddlers
The American journal of clinical nutrition, 2006Co-Authors: Xiao-yang Sheng, Rosalind S. Gibson, K. Michael Hambidge, Xi-xiang Zhu, Karl B. Bailey, Nancy F. KrebsAbstract:BACKGROUND Measurement of the major variables of Zinc Homeostasis is an essential prerequisite for estimating human Zinc requirements, which currently require a factorial approach. The data required for this approach have not been available for toddlers, whose requirements have been estimated by extrapolation from other age groups. OBJECTIVE The objective of the study was to measure key variables of Zinc Homeostasis in rural and small-town Chinese toddlers. DESIGN Zinc stable-isotope tracers were administered intravenously and orally with all meals for 1 d to 43 toddlers. Subsequent metabolic collections in the homes included duplicate diets, quantitative fecal collections, and spot urine sampling. Fractional absorption of Zinc (FAZ) was measured by a dual-isotope tracer ratio technique, and endogenous fecal Zinc (EFZ) was measured by an isotope dilution technique. RESULTS No group or sex differences were found. Therefore, results were combined for 43 toddlers aged 19-25 mo whose major food staple was white rice. Selected results (x+/- SD) were 1.86 +/- 0.55 mg total dietary Zn/d; 0.35 +/- 0.12 FAZ; 0.63 +/- 0.24 mg total absorbed Zn/d; 0.67 +/- 0.23 mg EFZ/d; and 65.0 +/- 8.3 microg plasma Zn/dL. The molar ratio of dietary phytate to Zinc was 2.7:1. CONCLUSIONS The mean intake and absorption of Zinc in this population are low in comparison with estimated average dietary and physiologic requirements for Zinc, and plasma Zinc values are consistent with Zinc deficiency. Intestinal losses of endogenous Zinc exceed previous estimates for toddlers, and only modest evidence exists of conservation in response to low Zinc intake and absorption.
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Zinc Homeostasis in Premature Infants Does Not Differ Between Those Fed Preterm Formula or Fortified Human Milk
Pediatric research, 2004Co-Authors: Sanju Jalla, Nancy F. Krebs, Donna J Rodden, K. Michael HambidgeAbstract:Zinc Homeostasis in Premature Infants Does Not Differ Between Those Fed Preterm Formula or Fortified Human Milk
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Zinc Homeostasis in Malawian children consuming a high-phytate, maize-based diet.
The American journal of clinical nutrition, 2002Co-Authors: Mark J. Manary, Christine Hotz, Nancy F. Krebs, Rosalind S. Gibson, Jamie E Westcott, Robin L. Broadhead, K. Michael HambidgeAbstract:Background: Zinc deficiency in children is an important public health concern in the developing world, and the consumption of predominantly cereal-based diets with a high phytate content may contribute to the risk. The gastrointestinal tract plays a central role in absorbing and conserving Zinc, yet it has not been carefully studied in such children. Objective: This study investigated Zinc Homeostasis in healthy, free-living Malawian children with habitually high-phytate diets to better understand the role of the gastrointestinal tract. Design: We evaluated Zinc Homeostasis in 10 children aged 2-5 y who were consuming a maize-based diet (phytate:Zinc molar ratio of 23:1). Zinc stable isotopes were administered orally and intravenously. The tracer and tracee were measured in urine and feces. Results: Endogenous fecal Zinc was high in comparison with results for this measure in previous studies. Typical correlations seen in subjects consuming a low-phytate diet between total absorbed Zinc, the size of the exchangeable Zinc pool, and endogenous fecal Zinc were not observed. Fractional absorption of Zinc was 0.24. Conclusions: Zinc Homeostasis was perturbed, particularly by large, endogenous fecal Zinc losses, in this vulnerable population. The effects of interventions to improve Zinc status, including dietary phytate reduction, on Zinc Homeostasis merit further study.
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Zinc Homeostasis during lactation in a population with a low Zinc intake
The American journal of clinical nutrition, 2002Co-Authors: Lei Sian, Nancy F. Krebs, Jamie E Westcott, Li Fengliang, Li Tong, Leland V. Miller, Bakary J. Sonko, Michael HambidgeAbstract:BACKGROUND There is a major increase in endogenous Zinc excretion, specifically via the mammary gland, in early human lactation. Whereas fractional absorption of dietary Zinc has been reported to increase in early human lactation, it is not known to what extent adaptive mechanisms may maintain Zinc Homeostasis, especially when dietary Zinc intake is relatively low. OBJECTIVE The objective of this study was to quantitate major variables of Zinc Homeostasis during early lactation in subjects from a population whose habitual dietary Zinc intake is low. DESIGN We studied 18 free-living lactating women from a rural community of northeast China whose infants were exclusively breast-fed. The subjects were studied at approximately 2 mo of lactation with use of stable isotopes of Zinc and metabolic collection techniques. Milk volume was measured with use of a deuterium enrichment method. RESULTS The mean (+/-SD) secretion of Zinc in milk was 2.01 +/- 0.97 mg/d, the intake of Zinc was 7.64 +/- 1.61 mg/d, and the fractional absorption of Zinc was 0.53 +/- 0.09, for a total daily Zinc absorption of 4.00 +/- 0.71 mg/d. Endogenous Zinc excretion in urine and feces was 0.30 +/- 0.10 and 1.66 +/- 0.97 mg/d, respectively. CONCLUSIONS Zinc balance, including Zinc secreted in breast milk, was maintained at approximately 2 mo of lactation in women whose habitual diet was low in Zinc. Homeostasis was achieved by high fractional absorption of Zinc and intestinal conservation of endogenous fecal Zinc.
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Interrelationships of key variables of human Zinc Homeostasis: relevance to dietary Zinc requirements.
Annual review of nutrition, 2001Co-Authors: Michael Hambidge, Nancy F. KrebsAbstract:Currently, estimates of human Zinc requirements depend primarily on a factorial approach. The availability of tracer techniques employing Zinc stable isotopes has facilitated the acquisition of data on major variables of Zinc Homeostasis in addition to those that can be measured with careful metabolic balance techniques. These data have promising potential to facilitate and improve the factorial approach. The thesis proposed in this paper is that realistic estimations of dietary Zinc requirements by a factorial approach require attention to the dynamic interrelationships between major variables of Zinc Homeostasis. This applies especially to the positive relationship between endogenous fecal Zinc and total absorbed Zinc, which is the essential starting point in estimating physiologic and, from there, dietary requirements.
Klaus D. Kröncke - One of the best experts on this subject based on the ideXlab platform.
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Heat shock but not cold shock leads to disturbed intracellular Zinc Homeostasis.
Journal of cellular physiology, 2010Co-Authors: Elvis Pirev, Yasemin Ince, Helmut Sies, Klaus D. KrönckeAbstract:The heat shock response is a highly conserved process essential for surviving environmental stress, including extremes of temperature. To investigate whether heat shock has an impact on intracellular Zn2+ Homeostasis, cells were subjected to heat shock, and subsequently the intracellular free Zinc concentration was investigated. Sublethal heat shock induced a temperature-dependent and transient intracellular Zn2+ release that was repeatable after 24 h. The free Zinc was localized in round-shaped nuclear bodies identified as nucleoli. Metallothionein, the main cellular Zinc storing protein, was found to be not functionally essential for this heat-shock-induced effect. No significant oxidative stress within the cells was detected after heat shock. Cold shock and subsequent rewarming did not result in disturbed intracellular Zinc Homeostasis. These results show that heat shock and cold shock differ with respect to intracellular Zn2+ release. A role for Zinc as signaling ion during fever is conceivable. J. Cell. Physiol. 223: 103–109, 2010. © 2009 Wiley-Liss, Inc.
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Ultraviolet-A irradiation but not ultraviolet-B or infrared-A irradiation leads to a disturbed Zinc Homeostasis in cells.
Free radical biology & medicine, 2008Co-Authors: Elvis Pirev, Helmut Sies, Christian Calles, Peter Schroeder, Klaus D. KrönckeAbstract:Abstract Changes of the redox balance in cells alter the availability of intracellular free Zn2+. Here, cells were exposed to ultraviolet (UV)-A, UV-B, or infrared (IR)-A light irradiation, and the intracellular free Zinc pool was monitored. Under sublethal conditions only UV-A irradiation resulted in a transient cytoplasmic and nuclear increase of intracellular free Zn2+. Likewise, tert-butyl hydroperoxide and singlet oxygen, but not H2O2 or intracellular generation of O2˙ˉ by redox cyclers, mimicked the effects of UV-A irradiation, while disulfide stress by diamide only led to a transient cytoplasmic Zinc release. These results show that only certain types of subtoxic cellular stress massively disturb the Zinc Homeostasis in cells.
Lothar Rink - One of the best experts on this subject based on the ideXlab platform.
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Influence of DNA-methylation on Zinc Homeostasis in myeloid cells: Regulation of Zinc transporters and Zinc binding proteins.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2016Co-Authors: Jana Elena Kessels, Lothar Rink, Hajo Haase, Inga Wessels, Peter UciechowskiAbstract:The distribution of intracellular Zinc, predominantly regulated through Zinc transporters and Zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular Zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed Zinc Homeostasis after DNA demethylation, the expression of human Zinc transporters and Zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) Zinc transporters revealed significantly enhanced mRNA expression of the Zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular Zinc levels. The mRNA expression of ZIP14 was decreased, whereas Zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated Zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of Zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore Zinc Homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting Zinc binding proteins and transporters, and, therefore, regulating Zinc Homeostasis in myeloid cells.
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Zinc Homeostasis and immunosenescence.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2014Co-Authors: Martina Maywald, Lothar RinkAbstract:For more than 50 years, Zinc is known to be an essential trace element, having a regulatory role in the immune system. Deficiency in Zinc thus compromises proper immune function, like it is observed in the elderly population. Here mild Zinc deficiency is a common condition, documented by a decline of serum or plasma Zinc levels with age. This leads to a dysregulation mainly in the adaptive immunity that can result in an increased production of pro-inflammatory cytokines, known as a status called inflamm-aging. T cell activation as well as polarization of T helper (Th) cells into their different subpopulations (Th1, Th2, Th17, regulatory T cells (Treg)) is highly influenced by Zinc Homeostasis. In the elderly a shift of the Th cell balance towards Th2 response is observed, a non-specific pre-activation of T cells is displayed, as well as a decreased response to vaccination is seen. Moreover, an impaired function of innate immune cells indicate a predominance of Zinc deficiency in the elderly that may contribute to immunosenescence. This review summarizes current findings about Zinc deficiency and supplementation in elderly individuals.
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Disturbed Zinc Homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of Zinc.
The Journal of nutritional biochemistry, 2012Co-Authors: Judith Jansen, Robertina Giacconi, Eugenio Mocchegiani, Eva Rosenkranz, Silke Overbeck, Sabine Warmuth, Ralf Weiskirchen, Wolfram Karges, Lothar RinkAbstract:Disturbances of Zinc Homeostasis have been observed in several diseases, including diabetes mellitus. To further characterize the association between Zinc and diabetes, we recruited 75 patients with type 1 or type 2 diabetes and 75 nondiabetic sex-/age-matched control subjects in order to analyze differences concerning human Zinc transporter 8 (hZnT-8) expression, single nucleotide polymorphisms (SNPs) in the genes of hZnT-8 as well as metallothionein 1A and serum/intracellular Zinc. Furthermore, we investigated the relation between insulin and Zinc Homeostasis in type 2 diabetic subjects and consolidated our results by in vitro analysis of the effect of insulin on cellular Zinc status and by analysis of the modulation of insulin signal transduction by intracellular Zinc Homeostasis. Concerning the expression of hZnT-8 and the SNPs analyzed, we did not observe any differences between diabetic and control subjects. Serum Zinc was significantly lower in diabetic patients compared to controls, and intracellular Zinc showed the same tendency. Interestingly, type 2 diabetes patients treated with insulin displayed lower serum Zinc compared to those not injecting insulin. In vitro analyses showed that insulin leads to an increase in intracellular Zinc and that insulin signaling was enhanced by elevated intracellular Zinc concentrations. In conclusion, we show that type 1 and type 2 diabetic patients suffer from Zinc deficiency, and our results indicate that Zinc supplementation may qualify as a potential treatment adjunct in type 2 diabetes by promoting insulin signaling, especially in Zinc-deficient subjects.
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cellular Zinc Homeostasis is a regulator in monocyte differentiation of hl 60 cells by 1α 25 dihydroxyvitamin d3
Journal of Leukocyte Biology, 2010Co-Authors: Svenja Dubben, Lothar Rink, Andrea Hönscheid, Katja Winkler, Hajo HaaseAbstract:It was reported previously that Zinc-deficient mice show impaired lymphopoiesis. At the same time, monocyte numbers in these animals are increased, indicating a negative impact of Zinc on monocyte development. Here, we investigate the role of Zinc Homeostasis in the differentiation of myeloid precursors into monocytes. Reduced gene expression of several Zinc transporters, predominantly from the Zip family, was observed during 1 alpha, 25-dihydroxyvitamin D(3) (1,25D(3))-induced differentiation of HL-60 cells. This was accompanied by a reduction of intracellular-free Zinc, measured by FluoZin-3. Amplifying this reduction with the Zinc chelator TPEN or Zinc-depleted cell-culture medium enhanced 1,25D(3)-induced expression of monocytic surface markers CD11b and CD14 on HL-60, THP-1, and NB4 cells. In contrast, differentiation of NB4 cells to granulocytes was not Zinc-sensitive, pointing toward a specific effect of Zinc on monocyte differentiation. Further, monocyte functions, such as TNF-alpha secretion, phagocytosis, and oxidative burst, were also augmented by differentiation in the presence of TPEN. The second messenger cAMP promotes monocyte differentiation. We could show that Zinc inhibits the cAMP-synthesizing enzyme adenylate cyclase, and chelation of Zinc by TPEN increases cAMP generation after stimulation with the adenylate cyclase activator forskolin. Based on our in vitro results and the in vivo observations from the literature, we suggest a model in which the intracellular-free Zinc concentration limits AC activity, and the decrease of Zinc after 1,25D(3) treatment promotes differentiation by relieving AC inhibition. Thus, cellular Zinc Homeostasis acts as an endogenous modulator of monocyte differentiation.
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Cellular Zinc Homeostasis is a regulator in monocyte differentiation of HL-60 cells by 1α,25-dihydroxyvitamin D3
Journal of leukocyte biology, 2010Co-Authors: Svenja Dubben, Lothar Rink, Andrea Hönscheid, Katja Winkler, Hajo HaaseAbstract:It was reported previously that Zinc-deficient mice show impaired lymphopoiesis. At the same time, monocyte numbers in these animals are increased, indicating a negative impact of Zinc on monocyte development. Here, we investigate the role of Zinc Homeostasis in the differentiation of myeloid precursors into monocytes. Reduced gene expression of several Zinc transporters, predominantly from the Zip family, was observed during 1, 25-dihydroxyvitamin D3 (1,25D3)-induced differentiation of HL-60 cells. This was accompanied by a reduction of intracellular-free Zinc, measured by FluoZin-3. Amplifying this reduction with the Zinc chelator TPEN or Zinc-depleted cell-culture medium enhanced 1,25D3induced expression of monocytic surface markers CD11b and CD14 on HL-60, THP-1, and NB4 cells. In contrast, differentiation of NB4 cells to granulocytes was not Zinc-sensitive, pointing toward a specific effect of Zinc on monocyte differentiation. Further, monocyte functions, such as TNF- secretion, phagocytosis, and oxidative burst, were also augmented by differentiation in the presence of TPEN. The second messenger cAMP promotes monocyte differentiation. We could show that Zinc inhibits the cAMP-synthesizing enzyme adenylate cyclase, and chelation of Zinc by TPEN increases cAMP generation after stimulation with the adenylate cyclase activator forskolin. Based on our in vitro results and the in vivo observations from the literature, we suggest a model in which the intracellular-free Zinc concentration limits AC activity, and the decrease of Zinc after 1,25D3 treatment promotes differentiation by relieving AC inhibition. Thus, cellular Zinc Homeostasis acts as an endogenous modulator of monocyte differentiation. J. Leukoc. Biol. 87: 000–000; 2010.
Christopher A. Mcdevitt - One of the best experts on this subject based on the ideXlab platform.
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ZnuA and Zinc Homeostasis in Pseudomonas aeruginosa
Scientific Reports, 2015Co-Authors: Victoria G. Pederick, Bart A. Eijkelkamp, Stephanie L. Begg, Miranda P. Ween, Lauren J. Mcallister, James C. Paton, Christopher A. McdevittAbstract:Pseudomonas aeruginosa is a ubiquitous environmental bacterium and a clinically significant opportunistic human pathogen. Central to the ability of P. aeruginosa to colonise both environmental and host niches is the acquisition of Zinc. Here we show that P. aeruginosa PAO1 acquires Zinc via an ATP-binding cassette (ABC) permease in which ZnuA is the high affinity, Zinc-specific binding protein. Zinc uptake in Gram-negative organisms predominantly occurs via an ABC permease and consistent with this expectation a P. aeruginosa Δ znuA mutant strain showed an ~60% reduction in cellular Zinc accumulation, while other metal ions were essentially unaffected. Despite the major reduction in Zinc accumulation, minimal phenotypic differences were observed between the wild-type and Δ znuA mutant strains. However, the effect of Zinc limitation on the transcriptome of P. aeruginosa PAO1 revealed significant changes in gene expression that enable adaptation to low-Zinc conditions. Genes significantly up-regulated included non-Zinc-requiring paralogs of Zinc-dependent proteins and a number of novel import pathways associated with Zinc acquisition. Collectively, this study provides new insight into the acquisition of Zinc by P. aeruginosa PAO1, revealing a hitherto unrecognized complexity in Zinc Homeostasis that enables the bacterium to survive under Zinc limitation.
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Overlapping Functionality of the Pht Proteins in Zinc Homeostasis of Streptococcus pneumoniae
Infection and immunity, 2014Co-Authors: Charles D. Plumptre, Bart A. Eijkelkamp, Christopher A. Mcdevitt, Catherine E. Hughes, Richard M. Harvey, James C. PatonAbstract:Streptococcus pneumoniae is a globally significant pathogen that causes a range of diseases, including pneumonia, sepsis, meningitis, and otitis media. Its ability to cause disease depends upon the acquisition of nutrients from its environment, including transition metal ions such as Zinc. The pneumococcus employs a number of surface proteins to achieve this, among which are four highly similar polyhistidine triad (Pht) proteins. It has previously been established that these proteins collectively aid in the delivery of Zinc to the ABC transporter substrate-binding protein AdcAII. Here we have investigated the contribution of each individual Pht protein to pneumococcal Zinc Homeostasis by analyzing mutant strains expressing only one of the four pht genes. Under conditions of low Zinc availability, each of these mutants showed superior growth and Zinc accumulation profiles relative to a mutant strain lacking all four genes, indicating that any of the four Pht proteins are able to facilitate delivery of Zinc to AdcAII. However, optimal growth and Zinc accumulation in vitro and pneumococcal survival and proliferation in vivo required production of all four Pht proteins, indicating that, despite their overlapping functionality, the proteins are not dispensable without incurring a fitness cost. We also show that surface-attached forms of the Pht proteins are required for Zinc recruitment and that they do not contribute to defense against extracellular Zinc stress.
Elvis Pirev - One of the best experts on this subject based on the ideXlab platform.
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Heat shock but not cold shock leads to disturbed intracellular Zinc Homeostasis.
Journal of cellular physiology, 2010Co-Authors: Elvis Pirev, Yasemin Ince, Helmut Sies, Klaus D. KrönckeAbstract:The heat shock response is a highly conserved process essential for surviving environmental stress, including extremes of temperature. To investigate whether heat shock has an impact on intracellular Zn2+ Homeostasis, cells were subjected to heat shock, and subsequently the intracellular free Zinc concentration was investigated. Sublethal heat shock induced a temperature-dependent and transient intracellular Zn2+ release that was repeatable after 24 h. The free Zinc was localized in round-shaped nuclear bodies identified as nucleoli. Metallothionein, the main cellular Zinc storing protein, was found to be not functionally essential for this heat-shock-induced effect. No significant oxidative stress within the cells was detected after heat shock. Cold shock and subsequent rewarming did not result in disturbed intracellular Zinc Homeostasis. These results show that heat shock and cold shock differ with respect to intracellular Zn2+ release. A role for Zinc as signaling ion during fever is conceivable. J. Cell. Physiol. 223: 103–109, 2010. © 2009 Wiley-Liss, Inc.
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Ultraviolet-A irradiation but not ultraviolet-B or infrared-A irradiation leads to a disturbed Zinc Homeostasis in cells.
Free radical biology & medicine, 2008Co-Authors: Elvis Pirev, Helmut Sies, Christian Calles, Peter Schroeder, Klaus D. KrönckeAbstract:Abstract Changes of the redox balance in cells alter the availability of intracellular free Zn2+. Here, cells were exposed to ultraviolet (UV)-A, UV-B, or infrared (IR)-A light irradiation, and the intracellular free Zinc pool was monitored. Under sublethal conditions only UV-A irradiation resulted in a transient cytoplasmic and nuclear increase of intracellular free Zn2+. Likewise, tert-butyl hydroperoxide and singlet oxygen, but not H2O2 or intracellular generation of O2˙ˉ by redox cyclers, mimicked the effects of UV-A irradiation, while disulfide stress by diamide only led to a transient cytoplasmic Zinc release. These results show that only certain types of subtoxic cellular stress massively disturb the Zinc Homeostasis in cells.
