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PubMed2005

Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.

BACKGROUND: The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects. AIMS: The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation. SUBJECTS: Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease. METHODS: Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting. RESULTS: The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc. CONCLUSIONS: These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.

Adult↗

PubMed1985

Growth, zinc and copper nutritional status of male premature infants with different zinc intake.

Zinc is an essential nutrient for growth and low intake can result in growth retardation. However, high zinc intake can affect copper metabolism. Therefore, data from a study of 10 male premature infants fed a cow's milk-based formula nonfortified with zinc (mean +/- SD = 1.4 +/- 0.1 mg X l-1) were compared with data of 10 similar infants fed the same formula fortified with zinc (4.1 +/- 0.3 mg X l-1). Growth, food intake, zinc and copper nutritional status were studied from 6 through 122 days of age. No differences in gain of weight, length and head circumference and in food intake were found. Serum zinc concentration was significantly (p less than 0.05) and hair zinc concentration was slightly higher in the infants fed the zinc-fortified formula at 122 days of age. Copper and ceruloplasmin concentrations in serum and hair copper concentration were similar in both groups at 122 days of age. The results suggest that feeding a formula nonfortified with zinc did not affect growth of male premature infants. Feeding a zinc-fortified formula on the other hand had no influence on copper nutritional status.

Copper↗

PubMed1987

Reduced leucocyte zinc and albumin-bound zinc in blood of haemodialysis patients.

The total, albumin-bound, and alpha 2-macroglobulin-bound zinc concentrations in serum samples obtained from 20 haemodialysis patients have been measured. Blood leucocyte zinc contents were also determined. The total serum zinc concentrations in these samples were low, and in each case this was due to reduction in the zinc associated with albumin, although the concentrations of albumin itself were normal. There was no abnormality of the zinc bound to alpha 2-macroglobulin. These data demonstrate a disturbance of the plasma transport of zinc in haemodialysis patients which might be due either to a reduced affinity of albumin for zinc in uraemic subjects, or the result of zinc deficiency. The zinc contents of white blood cells were also significantly reduced, supporting the possibility that these patients were indeed zinc deficient.

Adult↗

PubMed1987

Zinc-containing 7S-NGF complex. Evidence from zinc histochemistry for localization in salivary secretory granules.

7S-NGF is a pro-protein containing a neurotrophic subunit, beta-NGF, which has been localized by immunocytochemistry to the granules of granular convoluted tubule (GCT) cells in certain murine salivary glands [Watson et al., Anat Rec (1985) 213:365]. The 7S-NGF pro-protein contains zinc and is stabilized by zinc ions [Pattison and Dunn, Biochemistry (1976) 15:3696]. In the present work, dithizone, toluene sulfonamide quinoline (TSQ), and neo-Timm's methods for zinc were used to determine whether zinc histochemistry could be used to visualize the zinc associated with the 7S-NGF complex and, if so, whether zinc histochemistry might corroborate the reported localization of the 7S-NGF complex in GCT secretory granules. The results indicate that intensity of zinc staining varies with the reported variations in NGF levels in different salivary glands, and that the zinc is selectively concentrated in the GCT secretory granules. We suggest that zinc histochemistry may be a useful marker for the presence of the zinc-stabilized 7S-NGF pro-protein.

Animals↗

PubMed1989

Influence of marginal maternal zinc deficiency on pregnancy outcome and infant zinc status in rhesus monkeys.

To investigate the effects of marginal zinc deficiency on early development, rhesus monkeys were fed a diet marginally deficient in zinc (M; 4 micrograms/g) throughout pregnancy and during the first month of lactation. Despite the low concentration of zinc in the diet. M dams did not develop overt signs of zinc deficiency. However, compared to control dams fed diets adequate in zinc (C; 100 micrograms Zn/g), M dams showed a low response to the mitogens concanavalin A and phytohemagglutinin. Pregnancy outcome was similar in the two groups and all of the neonates were judged to be healthy at delivery. From birth until d 30 of age, the infants were closely monitored for signs of zinc deficiency, and at d 30, they were killed and tissues were removed and analyzed for a number of parameters reported to be affected by zinc status. At birth, M infants had low plasma zinc concentrations compared to controls; however, this difference was not observed at d 30. D 30 M infants showed a normal response to the mitogens concanavalin A and phytohemagglutinin, but showed a low response to pokeweed mitogen. Tissue (liver, brain, spleen, kidney, and heart) trace element concentrations were similar in the two groups of infants, as were liver metallothionein concentrations and 65Zn uptake/retention by isolated hepatocytes. Infant wt gain was inversely correlated with plasma zinc, liver zinc, and liver metallothionein concentrations in both the M and C groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Subcellular distribution of zinc in the benign and malignant human prostate: evidence for a direct zinc androgen interaction.

The subcellular distribution of zinc and its interaction with androgens has been examined in the benign and malignant human prostate. Endogenously, most of the zinc was associated with the nuclear fraction but significant concentrations were also found in the cytosol. Furthermore, the epithelium contained more zinc than that found in either the stroma or the intact gland. Zinc concentrations were lower in the subcellular fractions of the cancerous tissue when compared to hyperplastic specimens. In vitro uptake of zinc into prostatic homogenates was rapid and at equilibrium the binding was stable for both the 4 degrees C and the 37 degrees C incubations. At low zinc concentrations (less than or equal to 5 mM) the uptake was higher in the nucleus, whereas at higher concentrations, the cancerous tissue exhibited a greater capacity for the metal which was predominantly retained by the cytosol. Our data suggest the presence of a saturable zinc retention mechanism in the nucleus. The zinc uptake was found to be independent of any added androgen. In contrast, the total androgen uptake by prostate was significantly enhanced by the addition of zinc. This effect was not due to increases in the nuclear and cytosolic receptor binding since zinc inhibited the binding of the androgen to these receptors.

Cell Nucleus↗

PubMed2005

Zinc and zinc transporters in normal prostate and the pathogenesis of prostate cancer.

Zinc is an essential metal for all cells. It plays a role in a wide variety of physiological and biochemical processes. In the prostate epithelial cell the accumulation of high cellular zinc is a specialized function that is necessary for these cells to carry out the major physiological functions of production and secretion of citrate. The production of citrate and its secretion into prostatic fluid is a differentiated function of the prostate epithelial cells that is apparently important for reproduction. The loss of citrate and zinc accumulation is the most consistent and persistent characteristic of prostate malignancy. This characteristic of prostate cancer indicates that the lost ability of the malignant cells to accumulate zinc and citrate is an important factor in the development and progression of malignancy. The lost ability of the epithelial cells to accumulate zinc and thus to also accumulate citrate is the result of decreased expression of specific zinc uptake transporters. The purpose of this presentation is to review the current understanding of zinc and zinc homeostasis in the prostate and the role of zinc and zinc transporters in the normal function of the prostate and the pathogenesis of prostate cancer.

Biological Transport↗

PubMed1976

Effect of high amounts of dietary zinc and age upon tissue zinc in young chicks.

Weight gains of younger broiler chicks were not reduced by up to 2400 p.p.m. added zinc fed to four weeks of age. Tissue zinc was not changed significantly by 600 or 1200 p.p.m. supplemental dietary zinc, but at 2400 p.p.m. added zinc, blood, kidney, and liver zinc were significantly elevated (P less than 0.05). In the heart, zinc was not affected by the added dietary zinc but increased over time with all diets. Unlike the calf and weanling pig, the metabolism of zinc in the young chick does not appear to change appreciably with increasing maturity. Thus, the homeostatic control mechanisms of the young chick are effective for up to 1200 p.p.m. dietary zinc, but are partially overcome by 2400 p.p.m. added dietary zinc.

Age Factors↗

PubMed2001

Stimulatory effect of zinc and growth factor on bone protein component in newborn rats: enhancement with zinc and insulin-like growth factor-I.

The effect of zinc and growth factor on bone protein component in newborn rats was investigated. The characterization of protein component in the femoral-diaphyseal and metaphyseal tissue of newborn rats (3-35 days old) was examined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The diaphyseal and metaphyseal tissues of 7 days-old rats were cultured for 24 or 48 h in a medium containing either vehicle, zinc sulfate (10-4 M) or dipicolinate (10-3 M), a chelator of zinc ion, in the presence or absence of insulin-like growth factor-I (IGF-I; 10-8 M) or transforming growth factor-beta (TFG-beta; 10-10 M) with an effective concentration. Many cellular protein molecules were present in the diaphyseal and metaphyseal tissues; potent bands were seen in protein molecules with about 66 and 46 kDa. Protein molecule of about 66 kDa was greatly released in the medium cultured with the diaphyseal and metaphyseal tissues. This protein in the medium was increased by culture with zinc, IGF-I or TGF-beta. Total protein content in the medium cultured with the diaphyseal and metaphyseal tissues was significantly increased in the presence of zinc, IGF-I or TGF-beta. The IGF-I-increased medium protein content was significantly enhanced by zinc. This enhancing effect was not seen in TGF-beta. Alkaline phosphatase activity and deoxyribonucleic acid (DNA) content in the diaphyseal and metaphyseal tissues was significantly increased by culture with zinc, IGF-I or TGF-beta. The effect of IGF-I was significantly enhanced by zinc, while it was not found in TGF-beta. The effect of IGF-I or TGF-beta in increasing the bone components was seen in the presence of dipicolinate. This study demonstrates that zinc, like IGF-I and TGF-beta, can increase protein components in the femoral-diaphyseal and metaphyseal tissues of new-born rats. Zinc may especially play a role in bone growth in collaboration with IGF-I.

Alkaline Phosphatase↗

PubMed1977

Zinc metabolism in renal disease and renal control of zinc excretion.

Serum zinc concentrations are decreased in patients with a variety of clinical disorders including cirrhosis, nephrotic syndrome and renal insufficiency. Urinary zinc excretions are increased in the first two disease states. Symptoms of acute zinc deficiency (anorexia, dysfunction of smell and taste, and mental and cerebellar disturbances) and chronic zinc deficiency (growth retardation, anemia, testicular atrophy, and impaired wound healing) are common in these patients. It remains unresolved whether these disease states are indicative of true symptomatic or asymptomatic zinc deficiency or merely reflect a decrease in available zinc binding proteins. The low serum zinc concentrations and high urinary zinc excretions in patients with nephrotic syndrome do not appear to be due to loss of zinc bound to urinary proteins. Studies in dogs indicate increased serum and urine concentrations of certain amino acids(cysteine, histidine) greatly increase urinary zinc excretions. Studies are now underway to determine if the hyperzincuria and hypozincemia of cirrhosis, nephrotic syndrome and hyperalimentation can be explained by an increase in these urinary amino acids.

Animals↗

PubMed1981

Zinc deficiency and effects of zinc supplementation on sickle cell anemia subjects.

In this paper clinical similarities between sickle cell anemia patients and zinc deficient subjects, the latter as reported from the Middle East have been presented. Zinc levels in plasma, red cells, hair and neutrophils were decreased in our adult patients with SCA. The activities of certain zinc dependent enzymes such as plasma RNase, red cell carbonic anhydrase, leucocyte alkaline phosphatase, and deoxythymidine kinase activity in freshly synthesized collagen connective tissue were consistent with the concept that indeed zinc deficiency occurred in SCA patients. Zinc supplementation under controlled conditions showed that the SCA patients gained weight, their serum testosterone level increased and plasma ammonia level decreased. Finally, we also observed abnormal dark adaptation in some SCA patients which improved following zinc supplementation. Inasmuch as we have previously reported that the number of irreversible sickle cells decrease following zinc supplementation, we would like to suggest that zinc supplementation at earlier age may be benefical in preventing organ damage. In conclusion, zinc supplementation should be prescribed for patients with SCA, particularly if they show evidences for zinc deficiency.

Alkaline Phosphatase↗

PubMed1995

Limitations of zinc and metallothionein accumulation in rat livers following zinc administration.

In order to study whether or not there is a limit of zinc accumulation in livers of zinc-injected rats and establish the biosynthesis relationship of metallothionein by zinc, I examined the accumulated amount of zinc in rat liver after injection of ZnSO4 and the relationship between zinc and metallothionein contents in rat livers. Each rat was injected intraperitoneally once with 0.9% NaCl or zinc (10, 20, 40 or 60 mg zinc/kg b.w.) and was killed 14 h after injection. The distribution profiles of the hepatic cytosols of rats on a Sephadex G-75 column showed that the increased amounts of zinc were attributable to the metallothionein fraction. The zinc content in liver reached a maximum concentration of approx. 125 micrograms/g liver, corresponding to a dose (40 mg zinc/kg b.w.). These data suggested that there was a limit of zinc (essential metal) accumulation in livers of zinc-injected rats. The present results confirmed that the relative induction ability of metallothionein was mainly dependent on the metal content of the liver.

Animals↗

PubMed1978

Oral zinc therapy in geriatric patients with selected skin manifestations and a low plasma zinc level.

A geriatric population comprising 585 inhabitants of an institution for the aged was studied. Twenty-six persons with a mean age of 82 years were selected because of skin manifestations suggestive of chronic zinc deficiency. In 10 of the patients a subnormal plasma zinc level was found. This hypozincaemic group underwent a 4 week trial with zinc sulphate tablets, 0.6 g daily. The therapy failed to alleviate the skin condition in any of the patients, thus indicating that the changes were not caused by zinc deficiency. In the hypozincaemic group, plasma albumin was subnormal in all patients and significantly lower than in the normozincaemic subjects. The correlation between plasma zinc and plasma albumin levels in all 34 patients studied was highly significant (rs = 0.69, p less than 0.001). As plasma albumin tends to fall to subnormal concentrations with age, this explains why plasma zinc may be low in the elderly without indicating a state of zinc deficiency. After 2 and 4 weeks' zinc therapy, the mean plasma zinc concentration of the hypozincaemic group rose significantly from 9.5 to 17.6 and 23.4 mumol/1. This increase is higher than the rise observed in younger patients receiving an identical zinc sulphate dosage.

Aged↗

PubMed1995

Relative zinc-binding capacity of metallothionein in hepatic cytosols of zinc-injected rats.

In order to determine the zinc-binding capacity of metallothionein in hepatic cytosols of zinc-injected rats, we examined the relationship between zinc contents in cytosols and metallothionein fraction in rat livers. Each rat was injected intraperitoneally once with 0.9 % NaCl or zinc (10, 20, 40 or 60 mg zinc/kg b.w.) and was killed 14 h after injection. The distribution profiles of the hepatic cytosols of zinc-injected rats on a Sephadex G-75 column showed that the increased zinc was attributable to the metallothionein and high molecular weight proteins. Our results demonstrated that 63% of the increased zinc in hepatic cytosols of zinc-injected rats was bound to metallothionein and that 23% of the increased zinc was bound to high molecular weight proteins. These results suggest that the mechanisms of zinc accumulation in rat liver are different from those of cadmium accumulation.

Animals↗

PubMed1995

Relative zinc-binding capacity of metallothionein: studies in renal cytosols from zinc-injected rats.

Each rat was injected intraperitoneally once with 0.9% NaCl or zinc (10, 20, 40, or 60 mg zinc/kg b.w.). The zinc content in kidney reached a maximum level of approx. 50 microgram/g kidney, corresponding to a dose (40 mg zinc/kg b.w.). The distribution profiles of the renal cytosols of zinc-injected rats on a Sephadex G-75 column showed that most of the increased zinc was attributable to metallothionein. There was a linear relationship between the zinc contents in cytosol and metallothionein. Our results demonstrated that there was a limit of zinc accumulation in kidneys of zinc-injected rats and that 57% of the increased zinc in renal cytosols was bound to metallothionein. Our results suggest that the role of metallothionein in zinc accumulation in the kidney is similar to that of zinc accumulation in liver.

Animals↗

PubMed1977

Zinc, iron, copper, and magnesium concentrations in tissues of rats fed various amounts of zinc.

An experiment was conducted with rats to determine the effects on the tissue concentrations of Zn, Fe, Cu, and Mg of feeding various amounts of zinc. The rats were pair-fed one of the following diets for four weeks: Diet A, a zinc-deficient diet; a diet containing the recommended amoun of zinc (diet A plus 55 microgram of zinc per gram of diet), or diet A plus 550 microgram zinc per gram of diet. Concentrations of these elements in various tissues were determined by atomic absorption spectrometry after wet digestion. Feeding the rats zinc-supplemented diets resulted in increased zinc in blood, heart, kidney, and liver, and a marked decrease of iron in kidney and liver. Concentrations of the other two elements were unchanged in all tissues. Thus, the effect of zinc in decreasing iron concentrations in liver, observed by several investigators when rats were fed toxic amounts of zinc, also occurs when zinc is administered in normal or subtoxic amounts.

Animals↗

PubMed1998

[Supplementation with iron and folates during gestation: influence on the zinc status in the mother and on the zinc content in the maternal milk].

BACKGROUND: The aim of the present study was to investigate whether such supplementation impairs the zinc status of pregnant women or the zinc content of maternal milk. MATERIAL AND METHODS: Fifty seven women were studied during pregnancy and lactation. Zinc, iron and folate intakes were monitored during the third trimester of pregnancy using a five day food record and by registering intake of the same in the form of dietary supplements. Zinc levels were determined, using flame-atomic-absorption spectrophotometry, in serum during the third trimester of pregnancy, in transition milk (day 13-14 of lactation), and in mature milk (day 40 of lactation). RESULTS: 1.8% of pregnant women took zinc supplements whilst 7% took folate supplements. However, 100% of subjects showed zinc intakes (the sum of dietary and supplementary intakes) lower than those recommended. 87.7% showed the same for folate intake, 29.8% of pregnant women took iron supplements. When dietary and supplementary intakes were added, 26.3% of subjects showed iron intakes of over 200% of those recommended. Pregnant women with iron intakes in the third trimester of pregnancy of over 200% those recommended, showed lower serum zinc levels during the third trimester and, at a later date, lower mature milk zinc levels than did subjects with lower iron intakes. CONCLUSIONS: The combined dietary and supplementary intake of iron in some subjects provided total intakes of over 200% those recommended. Though this might be associated with an improvement in iron status it may impair those of zinc. Subjects with an intake of iron of over 200% of that recommended showed significantly lower serum and mature milk zinc levels than did those with lower iron intakes. It is suggested that the nutritional status of pregnant women should be carefully monitored and supplementation tailored to the needs of each individual.

Adolescent↗

PubMed2005

X-ray absorption fine structure analysis of the local environment of zinc in dentine treated with zinc compounds.

It has been reported that zinc oxide (ZnO) inhibits dentine demineralization. By using the X-ray absorption fine structure (XAFS) technique, our aims in this study were to provide information about the local environment of zinc atoms in dentine that had been treated with zinc compounds. We measured the Zn K-edge X-ray absorption near-edge structure (XANES) and the extended X-ray absorption fine structure (EXAFS) of dentine specimens treated with zinc chloride or ZnO. In XAFS analyses, the spectra of dentine specimens treated with ZnO (D-ZO) or with zinc chloride (D-ZC) were similar and obviously different from the reference ZnO spectrum. This suggests that most of the zinc atoms detected in D-ZO are not derived from particles of ZnO. The spectra of D-ZO and D-ZC were similar to the spectrum of the synthetic, zinc-containing hydroxyapatite, but were not similar to that of zinc in ZnCl2-treated collagen. The results of this study suggest that most of the zinc atoms detected were attached to hydroxyapatite and not to collagen.

Animals↗