Dietary zinc intake,supplemental zinc intake and serum zinc levels and the prevalence of kidney stones in adults

ObjectiveThe association between zinc intake and the risk of kidney stones remains controversial. We examined the associations between dietary zinc intake, supplemental zinc intake and serum zinc levels and the prevalence of kidney stones in adults.MethodsAdult participants from the 2007–2016 NHANES were included. Restricted cubic splines were adopted to assess the dose-response relationships.ResultsDietary zinc intake was linearly associated with the prevalence of kidney stones (P_{for non-linearity} = 0.50), and the odds ratios (95% confidence intervals) of kidney stones were 0.75 (0.51–1.04) for 10 mg/day, 0.65 (0.39-0.97) for 20 mg/day, 0.53 (0.30-0.94) for 30 mg/day and 0.45 (0.22-0.95) for 40 mg/day. The linear relationship was also observed among women and overweight/obese individuals. No association was found between supplemental zinc intake and the prevalence of kidney stones. A non-linear relationship was found between serum zinc levels and the prevalence of kidney stones (P_{for non-linearity} = 0.02), and the odds ratios (95% confidence intervals) of kidney stones were 0.52 (0.33-0.82) for 70 ug/dL, 0.43 (0.24-0.77) for 90 ug/dL, 0.56 (0.32-0.98) for 110 ug/dL and 0.77 (0.37–1.62) for 130 ug/dL. The non-linear relationship was also observed among men and overweight/obese individuals.ConclusionsDietary zinc intake and serum zinc levels were inversely associated with the prevalence of kidney stones in adults, and there may be effect modification by participant sex and body mass index. The present analysis is limited in its ability to establish causality.     

Phylogenetic analysis of the plant-specific zinc finger-homeobox and mini zinc finger gene families

Zinc finger-homeodomain proteins (ZHD) are present in many plants; however, the evolutionary history of the ZHD gene family remains largely unknown. We show here that ZHD genes are plant-specific, nearly all intronless, and related to MINI ZINC FINGER ( MIF ) genes that possess only the zinc finger. Phylogenetic analyses of ZHD genes from representative land plants suggest that non-seed plant ZHD genes occupy basal positions and angiosperm homologs form seven distinct clades. Several clades contain genes from two or more major angiosperm groups, including eudicots, monocots, magnoliids, and other basal angiosperms, indicating that several duplications occurred before the diversification of flowering plants. In addition, specific lineages have experienced more recent duplications. Unlike the ZHD genes, MIF s are found only from seed plants, possibly derived from ZHD s by loss of the homeodomain before the divergence of seed plants. Moreover, the MIF genes have also undergone relatively recent gene duplications. Finally, genome duplication might have contributed substantially to the expansion of family size in angiosperms and caused a high level of functional redundancy/overlap in these genes.     

Interaction of zinc and hemoglobin: binding of zinc and the oxygen affinity.

Stripped human hemoglobin was shown to have a high apparent zinc association constant of 1.3 X 10(7) M-1 with a stoichiometry of one zinc for every two hemes. The saturation of this site produces a dramatic 3.7-fold increase in the oxygen affinity. The effect of zinc on the oxygen affinity is interrelated with the interaction of 2,3-diphosphoglyceric acid (2,3-DPG) and hemoglobin. Thus, a smaller zinc effect is observed in the presence of added 2,3-DPG. Information about the location of the zinc-binding site responsible for the increased oxygen affinity has been obtained by comparing the binding of zinc to various hemoglobins. Blocking the beta93 sulfhydryl group decreases the apparent zinc association constant by an order of magnitude. The substitution of histidine-beta143 in hemoglobin Abruzzo [beta143 (H21) His leads to Arg] and hemoglobin Little Rock [beta143 (H21) His leads to Gln] decreases the apparent zinc association constant by two orders of magnitude. The substitution of histidine-beta143 by other amino acids and the reaction of the beta93 sulfhydryl group are known to produce dramatic increases in the oxygen affinity. The binding of zinc to one or both of these amino acids can, therefore, explain the zinc-induced increase in the oxygen affinity.     

Effects of the administration of cadmium and zinc on the concentration of zinc in the thymus of rats

The zinc content of thymus glands of male Wistar rats has been determined during five weeks of treatment with ZnCl₂ and CdCl₂, and compared with a group of control rats. THymus gland extracts were chromatographed on columns of Sephadex G-75 and the zinc content of the one hundred fractions obtained were determined by atomic absorption spectrophotometry. The rats treated with ZnCl₂ showed an increase in the thymus concentration of zinc bound to high and low molecular weight proteins. The rats treated with CdCl₂ showed an increase in zinc concentration, as opposed to the control group, during the first three weeks of treatment, and thereafter show a toxic effect of cadmium on the gland, with ulterior regression of the latter, and a decrease in the concentration of zinc.     

Changes in zinc ligation promote remodeling of the active site in the zinc hydrolase superfamily.

The zinc hydrolase superfamily is a group of divergently related proteins that are predominantly enzymes with a zinc-based catalytic mechanism. The common structural scaffold of the superfamily consists of an eight-stranded beta-sheet flanked by six alpha-helices. Previous analyses, while acknowledging the likely divergent origins of leucine aminopeptidase, carboxypeptidase A and the co-catalytic enzymes of the metallopeptidase H clan based on their structural scaffolds, have failed to find any homology between the active sites in leucine aminopeptidase and the metallopeptidase H clan enzymes. Here we show that these two groups of co-catalytic enzymes have overlapping dizinc centers where one of the two zinc atoms is conserved in each group. Carboxypeptidase A and leucine aminopeptidase, on the other hand, no longer share any homologous zinc-binding sites. At least three catalytic zinc-binding sites have existed in the structural scaffold over the period of history defined by available structures. Comparison of enzyme-inhibitor complexes show that major remodeling of the substrate-binding site has occurred in association with each change in zinc ligation in the binding site. These changes involve re-registration and re-orientation of the substrate. Some residues important to the catalytic mechanism are not conserved amongst members. We discuss how molecules acting in trans may have facilitated the mutation of catalytically important residues in the active site in this group.     

The relationship between the rate of chelator-induced zinc efflux from erythrocytes and zinc status

The rate of zinc (Zn) release from rat erythrocytes incubated in buffers containing a variety of chelators was measured. Only o-phenanthroline, 8-hydroxyquinoline-5-sulfonate, and EDTA caused detectable Zn release. The relationship between the rate of this release in the presence of o-phenanthroline and Zn status was determined in rats. Rats were fed one of the following: a modified AIN-76 diet providing 46 mumol (3 mg) Zn per kg of diet, a pair-fed diet providing 459 mumol (30 mg)/kg, or the previous diet fed ad lib. Animals were sacrificed at 2-wk intervals for 12 wk, and the Zn efflux rate, plasma, liver, and femur Zn concentrations were determined. The efflux rate was lower in erythrocytes taken from the rats fed the low-Zn diet. The efflux rate was also well correlated with femur Zn (r = 0.509, n = 98, p < 0.0001). A poorer correlation was observed with plasma Zn in the rats. Correlations also were determined between efflux rates and plasma Zn levels in human subjects. There was a significant correlation only in the males. In was concluded that the Zn efflux rate from erythrocytes incubated in the presence of o-phenanthroline is related to Zn status but is not sensitive enough to be a useful index of this status.     

Solubility of zinc and interactions between zinc and phosphorus in the hyperaccumulator Thlaspi caerulescens

The relationship between Zn and P in the Zn hyperaccumulator Thlaspi caerulescens J. & C. Presl was investigated using hydroponic culture. Total concentrations of Zn in the shoots increased from 0·2 to 27 g kg^–1 dry mass when solution Zn increased from 1 to 1000 mmol m^–3. Water-soluble Zn accounted for > 80% of the total Zn in the shoots containing > 5 g Zn kg^–1 dry mass. Total P was maintained at about 3 g kg^–1 dry mass in the shoots containing < 20 g Zn kg^–1 dry mass, but significantly decreased with higher Zn concentrations. Linear regression between insoluble P and insoluble Zn in the shoots produced a small slope, suggesting that co-precipitation of Zn and P was not an important detoxification mechanism in the shoots. In contrast, there was a strong correlation between insoluble P and insoluble Zn in the roots, with a linear slope of 0·3 — close to the P:Zn ratio in Zn₃(PO₄)₂. Foliar sprays of phosphate did not affect shoot dry mass significantly, but decreased root length and root dry mass significantly at Zn concentrations in solution from 10 to 3000 mmol m^–3. Foliar P was translocated to roots to enhance co-precipitation of Zn and P, although this did not enhance Zn tolerance. The results suggest that T.caerulescens possesses mechanisms which allow it to accumulate and sequester huge amounts of Zn in the shoots without causing P deficiency.     

Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals

Zinc(II) ions are essential for all forms of life. In humans, they have catalytic and structural functions in an estimated 3,000 zinc proteins. In addition, they interact with proteins transiently when they regulate proteins or when proteins regulate cellular zinc re-distribution. As yet, these types of zinc proteins have been explored poorly. Therefore the number of zinc/protein interactions is potentially larger than that given by the above estimate. Confronted with such a wide range of functions, which affect virtually all aspects of cellular physiology, investigators have begun to elucidate the molecular mechanisms of cellular homeostatic control of zinc, especially the functions of transporter, sensor, and trafficking proteins, such as metallothioneins, in providing the correct amounts of zinc ions for the synthesis of zinc metalloproteins. The sulfur-containing amino acid cysteine in proteins has an important role in the cellular mobility of zinc ions. Sulfur-coordination environments provide sufficiently strong interactions with zinc ions; they can undergo fast ligand-exchange; and they can serve as molecular redox switches for zinc binding and release. For the cellular functions of zinc, the free zinc ion concentrations (zinc potentials, pZn = −log[Zn²⁺]) and the zinc buffering capacity are critically important parameters that need to be defined quantitatively. In the cytoplasm, free zinc ions are kept at picomolar concentrations as a minute fraction of the few hundred micromolar concentrations of total cellular zinc. However, zinc ion concentrations can fluctuate under various conditions. Zinc ions released intracellularly from the zinc/thiolate clusters of metallothioneins or secreted from specialized organelles are potent effectors of proteins and are considered zinc signals. The cellular zinc buffering capacity determines the threshold between physiological and pathophysiological actions of zinc ions. When drugs, toxins, other transition metal ions or reactive compounds compromise zinc buffering, large zinc ion fluctuations can injure cells through effects on redox biology and interactions of zinc ions with proteins that are normally not targeted.

The influence of zinc status on the kinetics of zinc uptake into cultured endothelial cells

To better understand cellular zinc homeostasis and characterize the zinc transport process, a mammalian cell culture model was utilized to investigate the influence of zinc status on the kinetics of zinc uptake. Culturing conditions were optimized to induce moderate zinc deficiency and zinc excess while still sustaining the general health of the cells. Cells were grown in (1) control medium of 10% fetal bovine serum (FBS) in minimum essential medium (MEM; 5.0 micromol zinc/L), (2) low zinc medium (10% dialyzed FBS in MEM; 1.5 micromol zinc/L), or (3) zinc back medium (10% dialyzed FBS in MEM with zinc added as ZnCl(2); 5.0 micromol zinc/L). Bovine pulmonary artery endothelial cells (BPAEC), porcine aortic endothelial cells (PAEC), and porcine venous endothelial cells (PVEC) were evaluated as to their responsiveness to our zinc-deficient conditions. Zinc uptake was faster (P < 0.001) in all three cell types when they were grown in low zinc medium compared with controls; the increases were 32% in PAEC, 37% in PVEC, and 66% in BPAEC. Further kinetic analysis with BPAEC demonstrated a 31% increase (P < 0.05) in the maximum rate of zinc uptake (Jmax) grown in low zinc medium compared with controls, but no difference (P > 0.05) between the low zinc group and the control group in the concentration at which uptake was half-maximal (K). Zinc uptake into BPAEC grown in excess zinc conditions was not different (P > 0.05) unless the medium contained greater than 50 micromol zinc/L. In conclusion, BPAEC increased their ability for zinc uptake in response to moderate zinc deficiency, but did not change their kinetics of zinc uptake during moderate zinc excess.     

锌胁迫对彩色豆马勃体内锌的分布和活性形态及其抗氧化系统的影响

彩色豆马勃Pisolithus tinctorius可广泛与林木建立外生菌根,其共生可促进植物生长,提高植物对重金属的耐受性。然而,关于彩色豆马勃对重金属锌(Zn)胁迫的生理响应还不完全清楚。本研究在纯培养条件下,测定了Zn胁迫对彩色豆马勃生物量、Zn的活性形态和亚细胞分布,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和过氧化物酶(POD)活性,谷胱甘肽(GSH)、抗坏血酸(AsA)和黑色素含量的影响。结果表明,Zn胁迫抑制了彩色豆马勃的生长,在浓度为563 μmol/L时,达到半数最大抑制浓度(IC₅₀),在浓度为600 μmol/L时,生物量降低42.6%。Zn在彩色豆马勃中以活性较低的草酸盐、难溶于水的磷酸盐、果胶酸盐以及与蛋白质呈结合态或吸着态的形式为主。Zn胁迫显著提高了彩色豆马勃菌丝中CAT、POD和SOD活性,增加了GSH和黑色素含量,但对AsA的含量没有显著影响。本研究表明,彩色豆马勃主要通过调节Zn的分布及抗氧化系统,增加黑色素含量,增强对Zn的耐受性,为外生菌根真菌修复重金属污染土壤提供了理论支持。     

The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc regulation of the zinc transporters ZIP4 and ZIP5

The ZIP5 gene encodes a protein closely related to ZIP4, a zinc transporter mutated in the human genetic disorder acrodermatitis enteropathica. Herein, we demonstrate that mouse ZIP5 and ZIP4 genes are co-expressed in several tissues involved in zinc homeostasis (intestine, pancreas, embryonic yolk sac). However, unlike expression of the ZIP4 gene, which is induced during periods of zinc deficiency, ZIP5 gene expression is unaltered by dietary zinc. Immunohistochemistry localizes ZIP5 to the basolateral surfaces of enterocytes, acinar cells, and visceral endoderm cells in mice fed a zinc-adequate diet. However, this protein is removed from these cell surfaces and internalized during dietary zinc deficiency. In contrast, ZIP4 is induced and recruited to the apical surface of enterocytes and endoderm cells during zinc deficiency. In the pancreas, ZIP4 is expressed in beta-cells, whereas ZIP5 is expressed in acinar cells. These results suggest that the function of ZIP5 is antagonistic to that of ZIP4 in the control of zinc homeostasis; rather than functioning in the acquisition of dietary zinc, as does ZIP4, ZIP5 may function in the removal of zinc from the body. Thus, during periods when dietary zinc is replete, ZIP5 may function to remove zinc from the blood via the pancreas and intestine, the major sites of zinc excretion in mammals, whereas the acquisition of dietary zinc by intestinal ZIP4 would be minimal. In contrast, during periods of dietary zinc deficiency when secretion of zinc by the pancreas and intestine is minimized, ZIP5 is removed from the cell surface, and the intestinal uptake of zinc is augmented by induction of ZIP4.     

A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution

Many different zinc binding modules have been identified. Their abundance and variety suggests that the formation of zinc binding folds might be relatively common. We have determined the structure of CH1(1), a 27-residue peptide derived from the first cysteine/histidine-rich region (CH1) of CREB binding protein (CBP). This peptide forms a highly ordered zinc-dependent fold that is distinct from known folds. The structure differs from a subsequently determined structure of a larger region from the CH3 region of CBP, and the CH1(1) fold probably represents a nonphysiologically active form. Despite this, the fold is thermostable and tolerant to both multiple alanine mutations and changes in the zinc-ligand spacing. Our data support the idea that zinc binding domains may arise frequently. Additionally, such structures may prove useful as scaffolds for protein design, given their stability and robustness.