Functional characterization of the twin ZIP/SLC39 metal transporters, NpunF3111 and NpunF2202 in Nostoc punctiforme

The ZIP family of metal transporters is involved in the transport of Zn²⁺ and other metal cations from the extracellular environment and/or organelles into the cytoplasm of prokaryotes, eukaryotes and archaeotes. In the present study, we identified twin ZIP transporters, Zip11 (Npun_F3111) and Zip63 (Npun_F2202) encoded within the genome of the filamentous cyanobacterium, Nostoc punctiforme PCC73120. Sequence-based analyses and structural predictions confirmed that these cyanobacterial transporters belong to the SLC39 subfamily of metal transporters. Quantitative real-time (QRT)-PCR analyses suggested that the enzymes encoded by zip11 and zip63 have a broad allocrite range that includes zinc as well as cadmium, cobalt, copper, manganese and nickel. Inactivation of either zip11 or zip63 via insertional mutagenesis in N. punctiforme resulted in reduced expression of both genes, highlighting a possible co-regulation mechanism. Uptake experiments using ⁶⁵Zn demonstrated that both zip mutants had diminished zinc uptake capacity, with the deletion of zip11 resulting in the greatest overall reduction in ⁶⁵Zn uptake. Over-expression of Zip11 and Zip63 in an E. coli mutant strain (ZupT736::kan) restored divalent metal cation uptake, providing further evidence that these transporters are involved in Zn uptake in N. punctiforme. Our findings show the functional role of these twin metal uptake transporters in N. punctiforme, which are independently expressed in the presence of an array of metals. Both Zip11 and Zip63 are required for the maintenance of homeostatic levels of intracellular zinc N. punctiforme, although Zip11 appears to be the primary zinc transporter in this cyanobacterium, both ZIP’s may be part of a larger metal uptake system with shared regulatory elements.     

Zinc homeostasis in the secretory pathway in yeast

It is estimated that up to 10% of proteins in eukaryotes require zinc for their function. Although the majority of these proteins are located in the nucleus and cytosol, a small subset is secreted from cells or is located within an intracellular compartment. As many of these compartmentalized metalloproteins fold to their native state and bind their zinc cofactor inside an organelle, cells require mechanisms to maintain supply of zinc to these compartments even under conditions of zinc deficiency. At the same time, intracellular compartments can also be the site for storing zinc ions, which then can be mobilized when needed. In this review, we highlight insight that has been obtained from yeast models about how zinc homeostasis is maintained in the secretory pathway and vacuole.     

Strategies for Dendrite‐Free Anode in Aqueous Rechargeable Zinc Ion Batteries

Ongoing interest is focused on aqueous zinc ion batteries (ZIBs) for mass‐production energy storage systems as a result of their affordability, safety, and high energy density. Ensuring the stability of the electrode/electrolyte interface is of particular importance for prolonging the cycling ability to meet the practical requirements of rechargeable batteries. Zinc anodes exhibit poor cycle life and low coulombic efficiency, stemming from the severe dendrite growth, and irreversible byproducts such as H₂ and inactive ZnO. Great efforts have recently been devoted to zinc anode protection for designing high‐performance ZIBs. However, the intrinsic origins of zinc plating/striping are poorly understood, which greatly delay its potential applications. Rather than focusing on battery metrics, this review delves deeply into the underlying science that triggers the deposition/dissolution of zinc ions. Furthermore, recent advances in modulating the zinc coordination environment, uniforming interfacial electric fields, and inducing zinc deposition are highlighted and summarized. Finally, perspectives and suggestions are provided for designing highly stable zinc anodes for the industrialization of the aqueous rechargeable ZIBs in the near future.     

锌指类基因调控蛋白──生物无机化学和分子生物学发展的新领域

生命必需元素锌,除了以锌酶的形式,参与生物体的各类代谢过程外,近年来发现,锌还以各种锌蛋白的结构方式,包括锌指、锌纽、锌带和锌簇等,参与生物体的基因转录、复制及蛋白质的合成等各种基因调节和控制过程．联想到金属硫蛋白在锌的体内平衡中所扮演的角色,很有可能锌是通过金属硫蛋白和锌指类蛋白的逐级调控,成为生物体生长发育的调控中心．癌基因和人免疫缺陷病毒（HIV）的许多调节蛋白也具有锌指类结构,这给癌症和爱滋病的治疗提供了新思路．     

Serum extracellular superoxide dismutase activity as an indicator of zinc status in humans

The present study focused on whether serum extracellular superoxide dimutase (EC-SOD) activity can be used as a functional indicator of marginal zinc deficiency in humans. Subjects in this study were 444 healthy adults over 30 yr of age living a normal rural life in Kyunggi province, Korea. The mean dietary zinc intake of subjects obtained from one 24-h recall was 6.41 ± 4.35 mg and the average serum zinc concentration of the subjects was 11.06 ± 2.44 (μmol/L. Subjects were divided into three groups by serum zinc concentrations: adequate (serum zinc >10.7 (μmol/L), low (serum zinc 9.0–10.7 μmol/L), and very low (serum zinc <9.0 μmol/L) groups. A total of 50 subjects were selected from the three groups for analysis of EC-SOD activities. The EC-SOD activity of subjects increased with increasing serum zinc concentrations, and the activities of the three groups were significantly different as indicated by the Kruskal-Wallis test (p = 0.0239). Also, serum EC-SOD activities were significantly correlated with serum zinc concentrations (r = 0.289,p = 0.04). Serum EC-SOD activities, however, were not significantly correlated to the dietary zinc intakes. In conclusion, these results show that EC-SOD activities are decreased in subjects with low serum zinc concentrations and suggest that EC-SOD activity may be a functional indicator of zinc nutritional status in humans.     

血锌与肝锌,骨骼锌及肌肉锌的相关性研究

用~(65)Zn同位素示踪法研究了不同年龄LACA小鼠体内血锌与肝脏锌、骨骼锌及肌肉锌的相关性。实验结果表明,血锌的代谢与骨骼内锌及肌肉内锌的代谢有明显的相关关系,而与肝脏内锌代谢无相关关系;骨骼及肌肉中锌含量占全身锌含量的90％,上述结果提示血锌的监测可反映体内锌的水平。     

Intracellular zinc during cell activation and zinc deficiency

IntroductionZinc is an essential trace element having manifold functions within living cells. Zinc deficiency but also zinc excess impairs cell-specific functions whereas a balanced zinc level is required for an adequate cell behavior.Material and methodsThis study deals with the impact of cellular priming due to stimulation with interleukin (IL)-1, IL-2, IL-4, IL-6 or the chemokine CXCL12a and its subsequent influence on the intracellular free zinc concentration. Since cellular priming and activation is essential for proper immunological reactions, and across that highly cell-type specific, we investigated T cells, B cells, and peripheral blood mononuclear cells (PBMCs). Additionally, alterations of the intracellular zinc content was investigated by inducing zinc deficiency using the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) with subsequent re-supplementation of zinc, hence generating an intracellular zinc flux. Evaluation of zinc staining with FluoZin3-AM, Zinpyr-1 and Zinquin was done by flow cytometry or by fluorescence microscopy.ResultsOur results indicate that cellular priming for different periods of time (10 minutes/one hour) causes decreased intracellular free zinc concentrations in the FluoZin3-AM staining and increased zinc concentrations stained with Zinpyr-1. Furthermore, zinc supplementation after induced zinc deficiency leads to a fast and excessive rise of the intracellular free zinc levels in most cellular compartments.ConclusionOur study emphasizes the importance of zinc homeostasis and zinc distribution during cellular priming and for certain signaling cascades especially in T and B cells. Moreover, we demonstrated that zinc re-supplementation of zinc deficient cells results in significantly elevated intracellular free zinc concentrations compared to untreated controls. Hence, this underlines the need of a balanced zinc homeostasis for proper immune cell function.     

Zinc availability from zinc lipoate and zinc sulfate in growing rats

The purpose of this study was to investigate the effect of zinc lipoate and zinc sulfate on zinc availability in growing rats. 6 . 6 male albino rats were fed purified diets based on corn starch, egg albumen, sucrose, soy bean oil and cellulose over a 4-week period (diet Ia: 10 mg Zn/kg as zinc sulfate, diet Ib: 10 mg Zn/kg as zinc lipoate, diet IIa: 10 mg Zn/kg as zinc sulfate +0.4% phytic acid, diet IIb: 10 mg Zn/kg as zinc lipoate +0.4% phytic acid, diet IIIa: 20 mg Zn/kg as zinc sulfate + 0.4% phytic acid, diet IIIb: 20 mg Zn/kg as zinc lipoate + 0.4% phytic acid). Zinc lipoate and zinc sulfate both proved to be highly available zinc sources. When 0.4% phytic acid were present in the diets, apparent zinc absorption was generally depressed but was higher from zinc lipoate in tendency than from zinc sulfate. Comparable results were evident for femur zinc, plasma zinc and metallothionein concentrations in liver tissues. This indicates that zinc lipoate could be a valuable zinc source under conditions of low zinc availability. Nevertheless the absence or presence of phytic acid was a more important factor influencing zinc availability than the type of zinc source investigated.     

Zinc Casting and Recycling (8 pp)

Aim, Scope and Background Metal die casting is a highly energy-intensive industry. In addition to that, the production of primary zinc by smelting consumes huge amounts of energy as well as generates many types of pollution. This paper uses LCA to investigate the environmental performance of a zinc cast product. The areas of environmental concern are focused on the direct and indirect air emissions that arise from the Zinc Smelting, Casting and Recycling, as well as transportation. Main Features The LCA case study employs a cradle-to-gate approach, which starts with the purchasing of primary zinc from abroad, casting, inspection, and ends when the scrap metal is sent back for recycling by truck. Based on a “generic” zinc casting product, the objective of the LCA was to compare the air emissions from the material cycle due to: i) the increased content of recycled metal in the final cast product; and ii) the choice of selecting between two Remelters (A and B), the first located near the company and the other in a neighbouring country, to send zinc scrap for recycling. The LCA SimaPro software (version 5.0) Eco-indicator “99 method is used to perform an impact assessment for Climate Change, Acidification, Ecotoxicity, Respiratory Inorganics, and Respiratory Organics was performed. Results The results from direct (process) and indirect (power plants) air emissions confirmed that the major air pollution occurs during Zinc Smelting, that is up to approximately 65–70%. Although an increase in recycling rates resulted in higher levels of air pollution from transportation as well as heavy metals from dross, these two issues were insignificant compared to the huge amount of energy consumed for primary metal production. Based on air pollution from transportation alone, a significant reduction of greenhouse gases and VOCs of 90% each was appreciated when Remelter A was selected. Conclusion The results verified that efforts to recycle zinc and consume the material in a more sustainable manner have become highly important. Also, a second LCA investigation that was made to compare zinc cast products that consists of: 100% primary zinc, mixtures of 50–50% and 40–60% primary-to-recycled zinc, and finally 100% recycled zinc; further emphasized the need for using recycled metal, as opposed to using primary metal.     

Resveratrol–zinc combination for prostate cancer management

Zinc, an essential trace element, plays a critical role in cell signaling, and defect(s) in zinc homeostasis may contribute to adverse physiological and pathological conditions, including cancer. Zinc is present in healthy prostate at a very high concentration, where it is required for important prostatic functions. However, zinc levels are significantly diminished in cancerous tissue, and intracellular zinc level is inversely correlated with prostate cancer progression. During neoplastic transformation, zinc-accumulating, citrate-producing normal prostate cells are metabolically transformed to citrate oxidizing cells that lose the ability to accumulate zinc. Interestingly, zinc has been shown to function as chemopreventive agent against prostate cancer, albeit at high doses, which may lead to many adverse effects. Therefore, novel means to enhance bioaccumulation of sufficient zinc in prostate cells via increasing zinc transport could be useful against prostate cancer. On the basis of available evidence, we present a possibility that the grape antioxidant resveratrol, when given with zinc, may lead to retuning the zinc homeostasis in prostate, thereby abolishing or reversing malignancy. If experimentally verified in in vivo model(s) of prostate cancer, such as transgenic mouse models, this may lead to novel means toward management of prostate cancer and other conditions with compromised zinc homeostasis.     

Zinc kinetics in insulin-dependent diabetes mellitus patients

Zinc has an important role in the control of carbohydrate metabolism, and diabetic patients are at risk for zinc deficiency. However, there are conflicting data concerning nutritional zinc status. In order to investigate this topic, 10 normal and 10 insulin-dependent diabetic patients were studied following venous zinc tolerance test. Our results found no evidence of zinc deficiency or of changes on the kinetic parameters of zinc in patients with insulin-dependent diabetes mellitus following a venous zinc tolerance test.     

Plasma zinc response to a breakfast meal or fasting in elderly women

The aim of this study was to determine whether the postprandial decline in plasma zinc concentration is altered by aging. Eleven women, between the ages of 65 and 82 yr, participated in two separate experimental protocols: a high carbohydrate breakfast trial and a fasting trial. Plasma zinc concentrations were measured from blood samples obtained at 8∶00am (baseline fasting) and at 30-min intervals until 1∶00pm during each trial. Following the breakfast meal, plasma zinc concentrations declined 14% from 75±1 to 65±2 μg/dL (p<0.05), reaching a nadir 2.7±0.2 h after the meal. This decline was significantly (p<0.0001) greater than the 3.6% fall observed during the fasting trial. Postprandial changes in the plasma zinc concentrations were correlated with postprandial changes in serum glucose (r=−0.43,p<0.001), serum insulin (r=−0.17,p<0.01), and serum phosphorus(r=0.32,p<0.005). These data show that plasma zinc concentrations decline following food intake in elderly women in the same manner as previously described for younger adult women.     

Zinc homeostasis and functions of zinc in the brain

The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers, is important for zinc homeostasis in the brain. Zinc is supplied to the brain via both barriers. A large portion of zinc serves as zinc metalloproteins in neurons and glial cells. Approximately 10% of the total zinc in the brain, probably ionic zinc, exists in the synaptic vesicles, and may serve as an endogenous neuromodulator in synaptic neurotransmission. The turnover of zinc in the brain is much slower than in peripheral tissues such as the liver. However, dietary zinc deprivation affects zinc homeostasis in the brain. Vesicular zinc-enriched regions, e.g., the hippocampus, are responsive to dietary zinc deprivation, which causes brain dysfunctions such as learning impairment and olfactory dysfunction. Olfactory recognition is reversibly disturbed by the chelation of zinc released from amygdalar neuron terminals. On the other hand, the susceptibility to epileptic seizures, which may decrease vesicular zinc, is also enhanced by zinc deficiency. Therefore, zinc homeostasis in the brain is closely related to neuronal activity. Even in adult animals and probably adult humans, adequate zinc supply is important for brain functions and prevention of neurological diseases.     

Alfalfa genotypes differ in their ability to tolerate zinc deficiency

Response of 13 alfalfa (Medicago sativa L.) genotypes to varied Zn supply (+Zn: 2 mg kg⁻¹ soil, −Zn: no added Zn) was studied in a pot experiment under controlled environmental conditions. Plants were grown for four weeks in a Zn-deficient siliceous sandy soil. Plants grown at no added Zn showed typical Zn deficiency symptoms i.e. interveinal chlorosis of leaves, yellowish-white necrotic lesions on leaf blades, necrosis of leaf margins, smaller leaves and a marked reduction in growth. There was solute leakage from the leaves of Zn-deficient plants, while no solute leakage from Zn-sufficient plants. The ratios of P:Zn, Fe:Zn, Cu:Zn and Mn:Zn in Zn-deficient plants were extremely high compared with Zn-sufficient plants indicating disturbance of P:Zn, Fe:Zn, Cu:Zn and Mn:Zn balance within plant system by Zn deficiency. Genotypes differed markedly in Zn efficiency based on shoot dry matter production. Alfalfa genotypes also differed markedly in P:Zn ratio, Cu:Zn ratio and Fe:Zn ratio under —Zn treatment. The shoot dry weight, shoot:root ratio, chlorophyll content of fresh leaf tissue, solute leakage from the leaves, Zn uptake and distribution of Zn in shoots and roots were the most sensitive parameters of Zn efficiency. Zn-efficient genotypes had less solute leakage but higher shoot:root ratio and higher Zn uptake compared with Zn-inefficient genotypes. Under —Zn treatment, Zn-inefficient genotypes had less Zn partitioning to shoots (33–37%) and more Zn retained in roots (63–67%), while Zn-efficient genotypes had about equal proportions of Zn in roots (50%) and shoots (50%). This revised version was published online in June 2006 with corrections to the Cover Date.     

A short-term zinc-deficient diet decreases bone formation through down-regulated BMP2 in rat bone

We investigated the effects of a short-term dietary zinc deficiency on bone metabolism. Zinc deficiency increased the mRNA expression of zinc uptake transporters such as Zip1, Zip13, and Zip14 in bone. However, zinc deficiency might not maintain zinc storage in bone, resulting in a decrease in bone formation through downregulation of the expression levels of osteoblastogenesis-related genes.     

细菌锌离子调控体系与感染北大核心CSCD

锌(Zn)是生命体不可或缺的微量元素,对细菌和宿主同等重要。细菌体内锌离子稳态的维持依赖锌离子转运和调控体系。宿主通过限制锌离子或高锌离子中毒来控制细菌感染。为了在宿主体内生存,细菌必须表达高亲和力的锌离子转运系统,如ZnuABC,以获取足够的锌离子。由于锌与细菌大量的代谢和毒性通路密切相关,在细菌建立感染的过程中尤为重要,因此通过抑制锌离子转运系统来影响锌离子的稳态,将成为一个非常有发展前途的新型抗菌策略。     

Dry matter production and distribution of zinc in bread and durum wheat genotypes differing in zinc efficiency

Six bread wheat (Triticum aestivum cvs. Kiraç-66, Gerek-79, Aroona, ES 91-12, ES-14 and Kirkpinar) and four durum wheat (Triticum durum cvs. BDMM-19, Kunduru-1149, Kiziltan-91 and Durati) genotypes were grown under controlled environmental conditions in nutrient solution for 20 days to study the effect of varied supply of Zn (0 to 1 µM) on Zn deficiency symptoms in shoots, root and shoot dry matter production, and distribution of Zn in roots and shoots.Visual Zn deficiency symptoms, such as whitish-brown lesions on leaves, appeared rapidly and severly in durum wheats, particularly in Kiziltan-91 and Durati. Among the durum wheats, BDMM-19 was less affected by Zn deficiency, and among the bread wheats Kiraç-66, ES 91-12, Aroona and Gerek-79 were less affected than ES-14 and Kirkpinar.Under Zn deficiency, shoot dry matter production was decreased in all genotypes, but more distinctly in durum wheat genotypes. Despite severe decreases in shoot growth, root growth of all genotypes was either not affected or even increased by Zn deficiency. Correspondingly, shoot/root dry weight ratios were lower in Zn-deficient than in Zn-sufficient plants, especially in durum wheat genotypes.The distinct differences among the genotypes in sensitivity to Zn deficiency were closely related with the Zn content (Zn accumulation) per shoot but not with the Zn concentration in the shoot dry matter. On average, genotypes with lesser deficiency symptoms contained about 42% more Zn per shoot than genotypes with severe deficiency symptoms. In contrast to shoots, the Zn content in roots did not differ between genotypes. Shoot/root ratios of total Zn content were therefore greater for genotypes with lesser deficiency symptoms than for genotypes with severe deficiency symptoms (i.e. all durum wheat genotypes).The results suggest that the enhanced capacity of genotypes for Zn uptake and translocation from roots to shoot meristems under deficient Zn supply might be the most important factor contributing to Zn efficiency in wheat genotypes. The results also demonstrate that under severe Zn deficiency, Zn concentration in the shoot dry matter is not a suitable parameter for distinguishing wheat genotypes in their sensitivity to Zn deficiency.     

Determination of the major zinc fractions in human serum by ultrafiltration

In this paper we report a method for measuring ultrafiltrable zinc in human serum by electrothermal atomic absorption spectrophtometry. We show also that ultrafiltration permits to determine alpha-2 macroglobulin bound zinc and losely bound zinc if a strong zinc ligand (EDTA) is added to serum before ultrafiltration. This last fraction, after deduction of ultrafiltrable zinc, represents roughly all albumin bound zinc. In 20 controls we found that ultrafiltrable zinc amounted 0.311 μmol/L (S.D.=0.117 μmol/L), alpha-2 macroglobulin bound zinc 3.08 μmol/L (S.D.=0.221 μmol/L), and albumin bound zinc 12.11 μmol/L (S.D.=1.95 μmol/L). Our method needs only a small volume of serum, it is simple and rapid but also very accurate and reliable. The losely bound fraction is very dynamic and, representing the physiologically active part of serum zinc, it could be a good marker of zinc deficiency.     

Zinc depletion suppresses tumor growth in mice

The hypothesis that in tumor-bearing animals an increase of host hepatic zinc metallothionein (Zn-MT) causes a restriction of zinc in the tumor tissue was studied. Three types of tumors were induced in laboratory mice by cell transplant. Tumor growth appears to be inhibited under zinc-deficient conditions, even in cases where zinc deficiency was started after tumor cell transplant. The survival times of tumor-bearing mice were prolonged by administration of cadmium chloride, which induces the synthesis of a combined zinc-cadmium metallothionein derivative in the host liver, but not in the tumor tissue, leading to an increase of hepatic zinc in the treated animals. The uptake of⁶⁵Zn by the liver of Cd-treated, tumor bearing mice was significantly higher than that of controls whereas uptake of⁶⁵Zn by tumor cells was significantly higher in controls than in the treated animals. These results suggest that restriction of zinc intake suppresses tumor growth.