Metallothionein Expression Is Increased in Monocytes and Erythrocytes of Young Men during Zinc Supplementation , ,

Competitive Reverse Transcriptase–Polymerase Chain Reaction Shows That Dietary Zinc Supplementation in Humans Increases Monocyte Metallothionein mRNA Levels1–3

Metallothionein mRNA in Monocytes and Peripheral Blood Mononuclear Cells and in Cells from Dried Blood Spots Increases after Zinc Supplementation of Men

Effect of consuming hi-oleic peanuts on adiposity and cardiometabolic health

Metallothionein concentrations in erythrocyte lysates derived from human subjects were measured by an ELISA procedure. IgG obtained from serum of sheep injected with human metallothionein 1 was used in this competitive assay. Subjects were fed a semipurified zinc-deficient diet (0.7 mg of zinc per kg of diet) for an 8-day depletion period after 3 days of acclimation. Fasting plasma zinc concentrations were reduced approximately 7%. Metallothionein in the erythrocyte lysates was significantly decreased to 59% of the initial level by the end of the depletion period. Supplementation of these depleted subjects with zinc (50 mg) did not increase erythrocyte metallothionein levels within 24 hr. Daily supplementation of control subjects with zinc (50 mg/day) increased erythrocyte metallothionein to a 7-fold maximum within 7 days. These levels were reduced by 61% within 14 days after zinc supplementation was terminated. Incubation of rat [35S]metallothionein with human erythrocyte lysate showed a time-dependent increase in 35S soluble in 20% trichloroacetic acid, indicating degradation of the labeled protein, presumably via protease activity in the lysate. It is proposed that zinc supplementation induces erythrocyte metallothionein during erythropoiesis and that low zinc intake decreases synthesis and/or accelerates degradation of the protein in reticulocytes/erythrocytes. Metallothionein levels in erythrocytes may provide a useful index upon which to assess zinc status in humans.

Erythrocyte metallothionein (E-MT) is considered a promising index of zinc status in humans, since it may be more sensitive than other biochemical indices to changes in dietary zinc. However, conditions of high zinc demand with substantial redistribution of tissue zinc and specific changes in hormone profile, such as pregnancy, may have an influence on E-MT levels in addition to dietary zinc. In this study, we compared E-MT concentrations in relation to other biochemical zinc indices in healthy pregnant women at delivery (n = 40) and non-pregnant women (n = 22) with similar habitual dietary zinc intakes (average 13.3 mg/d). Pregnant women had lower serum zinc and albumin-bound serum zinc, but higher levels of alpha 2-macroglobulin-bound serum zinc than the nonpregnant women. Erythrocyte zinc (E-Zn) was similar in both groups, but E-MT (mean +/- SE) was slightly but significantly (p < 0.05) higher in the pregnant women (2.9 +/- 0.09 nmol/g protein) compared to nonpregnant women (2.6 +/- 0.06 nmol/g protein). A significant correlation was observed between E-MT and E-Zn in the nonpregnant women (r = 0.70; p < 0.001), consistent with the role of intracellular zinc in the regulation of metallothionein synthesis. However, such correlation was not observed in the pregnant women, suggesting that E-MT levels in pregnancy may be influenced by factors related to the pregnant state.

The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults (n=39) were randomised to zinc treatment (ZT), receiving 22mg Zn/day (n=19), or no treatment (NT) (n=20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT-2A gene expression and fold change were found to be higher in the ZT group (P=0.025 and P=0.016, respectively) compared to the NT group, specifically at Day 2 (40±18% increase from baseline, P=0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT-2A gene expression was correlated with changes in all zinc transporter expressions (r (2)=0.54, P=0.029); the change in ZIP1 expression emerged as a univariate predictor (P=0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions (P=0.030). Physical activity level was positively correlated with baseline ZIP7 expression (r=0.36, P=0.029). The present study shows that MT-2A expression is related to changing expression of zinc transporter genes, specifically ZIP1, in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins

Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review

Proteomic analysis shows the upregulation of erythrocyte dematin in zinc-restricted human subjects

Zinc

Development of a Plasma Zinc Concentration Cutoff to Identify Individuals with Severe Zinc Deficiency Based on Results from Adults Undergoing Experimental Severe Dietary Zinc Restriction and Individuals with Acrodermatitis Enteropathica

Zinc Supplementation Prevents Alcoholic Liver Injury in Mice through Attenuation of Oxidative Stress

Suspicions that mild zinc deficiency is common among the elderly cannot be confirmed or refuted because definitive indicators of zinc status are lacking. The goal of this study was to document the clinical responsiveness of parameters of zinc status in a group of older adults consuming a carefully controlled diet: first moderately low in zinc (3.97 mg/day for 15 days) and then high in zinc (28.19 mg/day for 6 days). Fifteen older adults (mean age = 66.6 yrs) volunteered to consume a marginally zinc-deficient diet for 15 days followed by 6 days of zinc repletion. Plasma concentrations of erythrocyte metallothionein and the enzyme 5'-nucleotidase, as well as levels of zinc, alkaline phosphatase, copper and ceruloplasmin were measured before and after zinc depletion and repletion. Plasma zinc levels were not altered during the study. Alkaline phosphatase (AP) values did not change in the expected direction, although a small decrease in AP following zinc repletion was statistically significant. Erythrocyte metallothionein results followed a pattern similar to that of alkaline phosphatase, little change, but a small, statistically significant drop after zinc repletion. As expected, there were no diet-associated changes in plasma copper and ceruloplasmin levels. In contrast, plasma concentrations of the enzyme 5'-nucleotidase decreased (p < 0.01) from 2.7 +/- 0.5 to 1.1 +/- 0.5 U during zinc depletion and increased (p < 0.05) to 2.2 +/- 0.4 U after 6 days of repletion. Mild zinc deficiency is difficult to detect. In this study, traditional indicators such as plasma zinc and alkaline phosphatase did not change as would be expected in response to alterations in zinc intake. Likewise, erythrocyte metallothionein did not respond to altered zinc intakes as expected but this factor may reflect long-standing or more severe zinc depletion and thus requires additional study. Activity of the enzyme 5'-nucleotidase appears responsive to acute changes in zinc intake; however, more work is needed to define how well these activities will reflect zinc intake in other types of subjects.

Coordinate expression and localization of iron and zinc transporters explain iron–zinc interactions during uptake in Caco-2 cells: implications for iron uptake at the enterocyte

Effects of dietary zinc supplement during lactation on maternal zinc plasma and milk zinc concentration through 5 months of lactation were examined. One hundred and thirty eight healthy lactating mothers received a weekly 100 mg elemental zinc supplement (ZS, n = 67) or placebo (PG, n = 71) starting one week postpartum in a double blind, randomized design. Milk and plasma zinc concentrations were determined by atomic absorption spectrophotometer. During the course of study, there was not a significantly difference between ZG and PG groups in dietary zinc and energy intake. The mean plasma zinc concentration at 1st week and 5th month were 134 +/- 49.1 and 115.6 +/- 23 microg dL(-1) (PV = 0.005) for PG group, respectively; that of the ZG group these figures were 124.9 +/- 52.8 and 121 +/- 27.1 microg dL(-1) (PV = 0.38), respectively. The mean serum alkaline phosphatase concentration at 1st week and 5th month were 94.8 +/- 37 and 92.6 +/- 29.9 iu L(-1) for PG group, respectively; that of the ZG group these fissures were 90.5 +/- 36 and 90 +/- 29 iu L(-1) (PV = 0.21), respectively. Milk zinc concentration declined significantly over the course of study for two groups, with the sharpest decline occurring during the first 2 months. The mean monthly zinc concentration of ZG group declined from 310 +/- 138 at 1st week to 118 +/- 64 microg dL(-1) at 5th month (declined by 52%). Corresponding means for PG group were 322 +/- 161 and 109 +/- 70 microg dL(-1) (declined by 60%), respectively. Milk zinc concentration significantly different between two groups at 3 and 4 months. A similar study, however, with different zinc dose and administration manner, in zinc marginal deficient lactating mothers is needed to assess the impact of zinc supplementation on milk zinc concentrations.