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PubMed2002

The KOX zinc finger genes: genome wide mapping of 368 ZNF PAC clones with zinc finger gene clusters predominantly in 23 chromosomal loci are confirmed by human sequences annotated in EnsEMBL.

The chromosome locations of 368 human Kruppel-type zinc finger (ZNF) PAC clones were physically mapped by FISH to human chromosomes in support of recent efforts of assigning KOX cDNAs (KOX1-KOX32) to zinc finger gene clusters. Recent mapping results were validated and confirmed by sequence comparisons to zinc finger gene sequences automatically annotated in EnsEMBL. In toto, 799 Kruppel-type zinc finger genes have been annotated in EnsEMBL of which 290 genes are found to encode KRAB domains. Sequence homologies of the zinc finger domains were used to establish phylogenic trees of KOX zinc finger genes as well as of all KRAB containing human zinc finger and KOX genes documenting the evolution of KRAB zinc finger genes late in primate evolution. A list of 368 assigned ZNF PAC clones is available under http://www.pzr.uni-rostock.de/supplements.

Base Sequence↗

PubMed2003

Effects of zinc histidine and zinc sulfate on natural human keratinocytes.

BACKGROUND: Zinc salts are widely used as food supplements and medicinal mineral supplementation. Zinc deficiency is associated with impaired skin conditions. The influence of zinc on skin functionality has been proven in clinical investigations. OBJECTIVE: Within the following study comparative in vitro experiments were performed to study the influence of zinc sulfate (ZnSO(4)) and zinc histidine (Zn(His)(2)) on the physiology of cultured natural human keratinocytes. METHOD: Proliferation of natural human keratinocytes was quantitatively assessed by measurement of 5-bromo-2-deoxyuridine (BrdU) incorporation against an oligomeric procyanidin as positive control. Differentiation was determined by monitoring involucrin formation. Cell viability and cytotoxicity were assessed by dimethylthiazolyldiphenyltetrazolium bromide (MTT) testing and quantification of lactate dehydrogenase. RESULTS: Neither keratin synthesis as a late marker of cell differentiation nor mitochondrial cell activity were influenced by either zinc compound. The synthesis of involucrin, an early marker of differentiation, was significantly increased by both zinc salts, ZnSO(4) being the more potent stimulator. Both zinc salts significantly increased cell proliferation, with the histidine complex being more potent. Effects were in the range of the positive control. Necrotic cell toxicity decreased significantly when Zn(His)(2) was added to the cells. CONCLUSION: Under in vitro conditions Zn(His)(2) is a strong proliferation inductor of keratinocytes with a better tolerability and a lower induction of differentiation behavior than ZnSO(4).

Cell Differentiation↗

PubMed1996

Prolactin (PRL) is a zinc-binding protein. I. Zinc interactions with monomeric PRL and divalent cation protection of intragranular PRL cysteine thiols.

PRL in secretory granules is osmotically inert. Previous studies by us and others have suggested that this is due in part to hormone oligomerization. Data suggest intermolecular disulfide bridges and/or intermolecular ionic interactions, as thiols, urea, and chelators increase monomerization of the majority of granule PRL. Because of the inhibitory effect of zinc on PRL release from isolated granules and the effects of zinc on the specific packing of PRL within granules, we examined the possibility that zinc contributed to the stability and/or oligomerization of intragranular PRL. To do this, we first analyzed zinc binding to purified monomeric rat PRL in solution. Zinc binding was demonstrated using the chromogenic chelator 5,5'-nitrilodibarbituric acid (murexide) and was confirmed by matrix-assisted, time of flight mass analysis. Because these spectrophotometric methods were not applicable for intragranular PRL studies, we tested the influence of zinc on granule PRL indirectly. As hormone free thiols were potentially formed during PRL oligomerization and storage, these were possible sites for hormone-divalent cation interactions. By derivatization of thiols with 4-vinyl pyridine and isolation of the carboxyterminal region of granule PRL, we found that a proportion of the cysteines 189 and 197 occurred as thiols and not disulfides. These thiols were only detectable when EDTA was present in the granule incubations. It is proposed that binding of zinc stabilizes the intermolecularly bonded storage form of PRL, in part by protection of hormone free thiols. Removal of the divalent cation and exposure of free thiols could be what initiates the thiol-disulfide interchange necessary for conversion of intermolecular to intramolecular disulfide bonds before exocytosis. Experimentally, both urea and EDTA could remove zinc, thus initiating monomerization and explaining how these agents as well as thiols achieve monomerization.

Amino Acid Sequence↗

PubMed2006

Acrodermatitis enteropathica: zinc therapy and possible identification of a carrier state through multiple hair zinc analyses over three decades.

We report on the successful use of repeated hair analyses over three decades to monitor zinc and copper status in two siblings with Acrodermatitis enteropathica who were treated with oral zinc sulfate beginning in 1975. Furthermore, we report for the first time that analysis of zinc in hair over a 30-yr period allows for the identification of individuals who might be heterozygous carriers of this autosomal recessive disease and who, therefore, would be expected to have hair zinc levels intermediate between normal, healthy individuals and those with Acrodermatitis enteropathica. Zinc treatment of the two patients with Acrodermatitis enteropathica resulted in remission of the signs and symptoms of the disease within the first month of therapy. However, any short-term interruption (typically, 7-10 d) in oral zinc resulted in an almost immediate relapse, with the reappearance of the skin lesions. We also document the inverse relationship that exists between zinc and copper through analysis of these metals in the scalp hair from the two patients, thus providing a tool for ensuring adequate copper intake in patients taking relatively high doses of zinc over a long period.

Acrodermatitis↗

PubMed1983

Changes in plasma zinc and urinary excretion of zinc after operation with extracorporeal circulation.

Sixteen adults undergoing cardiac surgery were studied with respect to postoperative levels of zinc in plasma and urinary excretion of zinc. The preoperative plasma concentrations of zinc were normal. On the first postoperative day the mean for the series had fallen from 15 to 7.2 mumol/l. A gradual rise followed, and on the fifth day all patients had plasma zinc above the lower limit of normal range. The urinary excretion of zinc was significantly increased on the first, second and fifth days after surgery. The mean total of zinc in the urine during five days was 67 mumol. The short-term fall in plasma zinc level had no discernible effect on wound healing. It was therefore apparently harmless and did not indicate a need for zinc supplementation.

Aged↗

PubMed2005

Relationship between zinc parameters and either body weight gain, protein intake or survival time in zinc-deficient rats.

This study was undertaken to examine the relationships between zinc parameters (serum alkaline phosphatase activity, and zinc concentration in serum and femur) and either body weight gain, protein intake or survival time in zinc deficient rats. Demineralized soy protein (DP) and alkali-treated soy protein (AP) were used as dietary protein sources in order to make zinc deficient diets (< 0.5 mg zinc/kg diet). The same diets (DP and AP diets) supplemented with lysine or cystine were also given freely to rats. Moreover, in other experiments, the above relationships were examined. During the early stages, a significant negative correlation between body weight gain and survival time in zinc-deficient rats was demonstrated. The significant negative correlation coefficient between protein intake and survival time increased gradually, and the maximum value of this correlation coefficient was higher than that between body weight gain and survival time. The significant correlations between protein intake and femur zinc concentration were recognized throughout the longer periods. These results show that the number of zinc-deficient rats which survive decreases as protein intake increases throughout the feeding period, that the influence of protein intake is greater than that of body weight in early stages, and that the zinc requirements of rats rise with the increase in protein intake.

Alkaline Phosphatase↗

PubMed1975

Effects of high but nontoxic dietary zinc on zinc metabolism and adaptations in rats.

The effects of feeding a high but nontoxic zinc level to young rats for varied time periods on zinc metabolism and adaptations were investigated. Adding 600 ppm supplemental zinc to a "corn-soy" diet for periods from 7 to 42 days did not materially affect stable zinc level in any tissue studied. However, in every tissue, 65Zn retention from a single oral dose declined sharply with duration of added zinc feeding to 21 days, indicating a continuing adaptation in zinc metabolism for at least this period of time. Likewise, fecal 65Zn excretion increased with length of feeding time on high zinc, indicating a continuing reduction in net absorption for most of the 42-day period. When the data are compared with similar previous cattle studies, it is evident that there are major qualitative differences in zinc metabolism and homeostatic control between rats and cattle.

Animals↗

PubMed1992

Zinc salts effects on granulocyte zinc concentration and chemotaxis in acne patients.

To explore the mechanism by which zinc acts on cutaneous inflammatory lesions, we studied granulocyte zinc levels and in vitro polymorphonuclear leukocyte chemotaxis in 20 acne patients before and after 2 months of zinc therapy (200 mg/day zinc gluconate). The zinc level was assayed by flame absorption spectrophotometry and chemotaxis was performed by agarose assay. After 2 months of treatment, a significant decrease in granulocyte zinc level associated with inhibition of chemotaxis (r = 0.69) was observed in 16 patients. This suggests that zinc anti-inflammatory action is related to inhibition of polymorphonuclear leukocyte chemotaxis induced by a decreased granulocyte zinc level.

Acne Vulgaris↗

PubMed2000

Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter.

The yeast ZRT1 zinc transporter is regulated by zinc at both transcriptional and post-translational levels. At the post-translational level, zinc inactivates ZRT1 by inducing the removal of the protein from the plasma membrane by endocytosis. The zinc transporter is subsequently degraded in the vacuole. This regulatory system allows for the rapid shut off of zinc uptake activity in cells exposed to high zinc concentrations, thereby preventing overaccumulation of this potentially toxic metal. In this report, we examine the role of ubiquitin conjugation in this process. First, we show that ZRT1 is ubiquitinated shortly after zinc treatment and before endocytosis. Secondly, mutations in various components of the ubiquitin conjugation pathway, specifically the RSP5 ubiquitin-protein ligase and the UBC4 and UBC5 ubiquitin conjugating enzymes, inhibit both ubiquitination and endocytosis. Finally, mutation of a specific lysine residue in ZRT1 blocks both ubiquitination and endocytosis. This critical lysine, Lys-195, is located in a cytoplasmic loop region of the protein and may be the residue to which ubiquitin is attached. These results demonstrate that ubiquitin conjugation is a critical step in the signal transduction pathway that controls the rate of ZRT1 endocytosis in response to zinc.

Biological Transport↗

PubMed1976

Zinc content and the zinc-to-calorie ratio of weighed diets.

The zinc content of weighed, self-selected diets of high school girls and college women varied widely. A majority of the diets contained less than the 15-mg. recommended allowance for zinc and a significant number provided less than two-thirds of the allowance. Approximately one-third of thirty diets planned and prepared for a metabolic study contained less than 10 mg. zinc. The zinc content of the metabolic diets appeared to reflect the kind of meat included. Zinc-to-calorie ratios of the self-selected diets were 8.6 and 8.8 mg. per 1,000 kcal for high school girls and college women, respectively. The metabolic diets provided a mean of 6.6 mg. zinc per 1,000 kcal. Consideration of the energy values and the zinc-to-calorie ratios of these diets suggests that energy restriction and choice of foods are important factors contributing to zinc intakes below the recommended amount.

Adolescent↗

PubMed1978

Changes in serum zinc and copper induced by operative trauma and effects of per- and postoperative zinc infusion.

Serum zinc, albumin and copper levels were monitored for 5 days after operative trauma in 22 patients. As in earlier studies, a decrease in serum zinc and albumin levels was found. The mean fall in serum zinc was 40% and in albumin, 20%, of the preoperative values. Serum zinc increased after postoperative day 2; albumin remained decreased, indicating a rise in filtrable zinc. A correlation between the fall in serum albumin and serum zinc was found in individual patients. In contrast to previous studies, we found a decrease in serum copper postoperatively. A further 23 patients were supplemented with a zinc and copper containing infusion per- and postoperatively. These patients showed a marked (significant) reduction in the serum zinc fall, the serum level being normalized after 5 days. An insignificant reduction in the fall of serum albumin was also found.

Copper↗

PubMed1997

Zinc and platelet membrane microviscosity in Alzheimer's disease. The in vivo effect of zinc on platelet membranes and cognition.

OBJECTIVES: To investigate the effects of oral zinc supplementation on: (i) plasma zinc concentrations; (ii) platelet membrane microviscosity in vivo; and (iii) cognitive function of Alzheimer's disease (AD) patients. DESIGN: An open-labelled pilot study. SETTING: University of Stellenbosch Medical School and Stikland Hospital. SUBJECTS: Six volunteer AD patients. OUTCOME MEASURES: Plasma zinc levels, platelet membrane microviscosity and cognition (MMSE and ADAS-cog tests). RESULTS: Oral zinc supplementation (30 mg/day) did not increase plasma zinc levels significantly, but significantly increased platelet membrane microviscosity (P = 0.02; 6 patients). Four patients, who underwent 12 months of evaluation, showed modest cognitive improvement on psychometric testing (Mini-Mental State Examination and the cognitive portion of the Alzheimer's Disease Assessment scale scores). CONCLUSIONS: While earlier literature promoted the use of zinc in AD patients, a recent study has contradicted this and implicated zinc in the aetiology of Alzheimer's disease. On the basis of the above results, it may be premature to single out zinc as a causal agent in AD.

Aged↗

PubMed1990

A new zinc compound, beta-alanyl-L-histidinato zinc, stimulates bone growth in weanling rats.

The effect of a new zinc compound. beta-alanyl-L-histidinato zinc (AHZ), on bone metabolism in weanling rats was investigated. Rats were orally administered AHZ (0.5-2.5 mg/100 g body weight) for 3 days, and 24h later they were killed. Administration of AHZ (1.0 and 2.5 mg/100 g) caused a significant increase of zinc content in the femoral diaphysis and a corresponding elevation of calcium content, alkaline phosphatase activity, and DNA content. A dose of 0.5 mg/100g AHZ did not produce an appreciable increase in bone components. When zinc sulfate (0.55 mg Zn/100g) was orally administered in rats for 3 days, the bone zinc content, calcium content, and alkaline phosphatase activity were raised significantly, but bone DNA content was not appreciably affected. Thus, the stimulation of AHZ (2.5 mg/100g), which corresponds to 0.55 mg Zn/100g, on bone metabolism was more intensive than that of zinc sulfate. These results suggest that AHZ can stimulate bone growth in weanling rats, and that the compound has a greater effect in comparison with zinc sulfate.

Alkaline Phosphatase↗

PubMed1981

[Studies on the setting reaction of the zinc phosphate dental cement (3)--quantitative analysis for consumed zinc oxide through setting reaction of the cement (author's transl)].

Zinc oxide powder of zinc phosphate cement for dental use was mixed with various phosphoric acid for cement liquid contained Al3+ and not, and zinc oxide in each cement after setting was determined quantitatively Then, consumed zinc oxide through setting reaction was calculated. When zinc oxide powder was mixed with cement liquid contained Al3+, consumed zinc oxide through setting reaction was approximate half quantity of it mixed with liquid contained no Al3+. This result show that setting reaction of zinc phosphate dental cement is the interaction Al3+ and H2PO4- in cement liquid rather than simple neutralizing reaction, ZnO+H3PO4 or ZnO+H2PO4-.

Aluminum↗

PubMed2002

Study of pH-dependent zinc(II)-carboxamide interactions by zinc(II)-carboxamide-appended cyclen complexes (cyclen = 1,4,7,10-tetraazacyclododecane).

To elucidate intrinsic recognition of carboxamides by zinc(II) in carbonic anhydrase (CA) (as inhibitors) and carboxypeptidase A (CPA) (as substrates), a new series of Zn(2+)-carboxamide-appended cyclen complexes have been synthesized and characterized (cyclen = 1,4,7,10-tetraazacyclododecane). Two types of Zn(2+)-carboxamide interactions have been found. In the first case represented by a zinc(II) complex of carbamoylmethyl-1,4,7,10-tetraazacyclododecane (L(1)), the amide oxygen binds to zinc(II) at slightly acidic pH (to form ZnL(1)), and the deprotonated amide N(-) binds to zinc(II) at alkaline pH (to form ZnH(-1)L(1)) with pK(a) = 8.59 at 25 degrees C and I = 0.1 (NaNO(3)), as determined by potentiometric pH titrations, infrared spectral changes, and (13)C and (1)H NMR titrations. The X-ray crystal structure of ZnH(-1)L(3) (where L(3) = N-(4-nitrophenyl)carbamoylmethyl cyclen, pK(a) = 7.01 for ZnL(3) <==> ZnH(-1)L(3)) proved that the zinc(II) binds to the amidate N(-) (Zn-N(-) distance of 1.974(3) A) along with the four nitrogen atoms of cyclen (average Zn-N distance 2.136 A). Crystal data: monoclinic, space group P2(1)/n (No. 14) with a = 10.838(1) A, b = 17.210(2) A, c = 12.113(2) A, b = 107.38(1) degrees, V = 2156.2(5) A(3), Z = 4, R = 0.042, and R(w) = 0.038. These model studies provide the first chemical support that carboxamides are CA(-) inhibitors by occupying the active Zn(2+) site both in acidic and alkaline pH to prevent the occurrence of the catalytically active Zn(2+)-OH(-) species. In the second case represented by a zinc(II) complex of 1-(N-acetyl)aminoethylcyclen, ZnL(6), the pendant amide oxygen had little interaction with zinc(II) at acidic pH. At alkaline pH, the monodeprotonation yielded a zinc(II)-bound hydroxide species ZnL(6)(OH(-)) (pK(a) = 7.64) with the amide pendant remaining intact. The ZnL(6)(OH(-)) species showed the same nucleophilic activity as Zn(2+)-cyclen-OH(-). The second case may mimic the Zn(2+)-OH(-) mechanism of CPA, where the nucleophilic Zn(2+)-OH(-) species does not act as a base to deprotonate a proximate amide.

Journal Article↗

PubMed1995

Chemotherapy for giardiasis: randomized clinical trial of bacitracin, bacitracin zinc, and a combination of bacitracin zinc with neomycin.

This study describes a prospective, randomized, clinical trial in patients infected with the protozoa Giardia lamblia. Patients received a 10-day treatment with twice a day doses of either 120,000 U (USP) of bacitracin zinc, 120,000 U (USP) of bacitracin, 120,000 U (USP) of neomycin, or 60,000 U (USP) of bacitracin zinc and 60,000 U (USP) of neomycin. At the first assessment (day 11), all 21 subjects (100%) treated with bacitracin zinc had ceased to show Giardia parasites in their stools compared with 19 (95%) of 20 receiving bacitracin, 20 (90.9%) of 22 subjects receiving neomycin, and 17 (89.5%) of 19 subjects receiving bacitracin zinc plus neomycin. During the two-week follow up period, one (5.3%) of the 19 subjects examined who received bacitracin zinc experienced a recurrence compared with one (6.7%) of 15 receiving bacitracin, one (5.0%) of 20 receiving neomycin, and 0 (0%) of 14 receiving the combination treatment. Final cure rates of 94.7% for bacitracin zinc, 87.5% for bacitracin, 86.4% for neomycin, and 87.5% for bacitracin zinc plus neomycin were obtained. No synergistic activity was noted between bacitracin zinc and neomycin. Side effects were generally limited to nausea, abdominal discomfort, and diarrhea in a small number of patients.

Adolescent↗

PubMed2002

Bioavailability of zinc in fiber-enriched bread fortified with zinc sulphate.

The present study aimed to reduce the caloric value of bread by substituting a part of wheat flour with artichoke bracts at levels of 5%, 10% and 15% without sacrificing taste, texture or acceptability. Moreover, considerable trials had been made to reduce zinc deficiency in wheat bread and fiber-enriched bread and also to study the effect of fiber on zinc bioavailability. Therefore, zinc sulphate was added to bread at levels of 40, 60, 80, 100 and 120 mg/100 g edible portion. The results from this study show that: (i) The addition of artichoke bracts to wheat flour increased the water absorption, arrival time, development time, and weakening of the dough as the level of artichoke bracts increased, while dough stability decreased. (ii) Mixing wheat flour with increasing amount of artichoke bracts increased the content of protein, fiber and total essential amino acids, also all essential amino acids increased in wheat bread and fiber-enriched bread after fortification with zinc sulphate at a level of 100 mg/100 g edible portion except methionine, threonine and tyrosine. (iii) The best level of zinc sulphate to give the best bioavailability for zinc is 100 mg/100 g edible portion. (iv) Evaluation of fortified wheat bread and fiber-enriched bread with zinc sulphate showed no significant difference by test panel.

Animals↗

PubMed2005

Therapeutic efficacy of zinc sulphate used in clustered model treatment in alleviating zinc deficiency in cattle and its effect on hormones, vitamins and production parameters.

A survey was conducted in 10 districts of northern India. Significant deficiency of zinc was observed in soil, fodders and (cattle) serum samples. The animals showed typical signs of zinc deficiency, namely stiff gait, swelling of hocks and knees, subcutaneous fluid accumulation, rough coat, etc. of variable intensity. A clustered model therapeutic trial was conducted and zinc-deficient cattle were divided into three groups. Group A was provided with mineral mixture containing zinc sulphate. Group B was given mineral mixture without zinc sulphate and group C was given no mineral mixture. Significant improvement (p < 0.01) was observed in the haemoglobin (Hb), total white blood cells (WBC) and total erythrocyte count (TEC) levels at the 7th day of treatment in the animals of group A. Significant improvement in enzyme serum alkaline phosphatase (SAP) was observed in group A animals at the 7th day, while improvement in asparatate aminotransferase (AST), alanine aminotransferase (ALT) and ceruloplasmin (Cp) was observed after 21 days of treatment. Regarding hormones, significant improvement was observed in thyroxine (T3) and triiodothyronine (T4), oestrogen and progesterone in group A animals within 14 days of treatment. The values of vitamin A showed a highly significant (p < 0.01) improvement within 7 days of treatment in group A animals and that of vitamin E on the 21 st day of treatment. The milk yield of lactating cattle and body weight of growing calves in group A showed highly significant (p < 0.01) increases at about 14 and 30 days, respectively. It is concluded that zinc sulphate supplementation is highly effective in alleviating zinc deficiency and improving various biochemical and production parameters in cattle. The clustered model treatment provides a better indicator of the most limiting element under field conditions where simultaneous deficiency of various minerals is prevalent.

Alanine Transaminase↗