• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.292-298
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• 2007

Zinc plays indispensable roles in metabolism, including cell growth, apoptosis, proliferation and differentiation. Kidneys are target organs for various regulators of mineral metabolism, and play a key role in zinc balance. To investigate the zinc uptake efficiency, we examined the zinc uptake and accumulation level in vivo and in vitro study. Plasma zinc concentration was peaked out at 1 hr after oral zinc administration. The renal zinc level was peaked out at 12 hr after oral zinc administration, and it was the highest in 40 mg/kg Zn-Asp administrated group in comparison with other groups. In addition, the m-RNA expression level of zinc transporter-1 (ZnT-1), zinc transporter-2 (ZnT-2) and high-affinity L-aspartate transporter (EAAT-3) in Zn-Asp administered group were increased compared with control groups and $ZnSO_4$ group. In order to investigate the intracellular zinc uptake mechanism, we performed the in vitro study by using human embryonic kidney cell line, HEK 293. Intracellular zinc level was peaked out at 3 hr after zinc treatment. In the same way, the mRNA expression level of ZnT-1 and EAAT-3 were increased compared with control group. This study showed that Zn-Asp is effective the zinc uptake into the kidney by increasing the zinc transporter expression.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.132-136
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• 2007

Zinc is essential metal and plays a role in a wide variety of physiological and biochemical processes. Prostate gland contains high level of zinc, generally 3-10 folds higher than other organs. Prostatic zinc uptake is resulted from the existence of zinc transporter (ZnT) protein families in membrane. In this study, we investigated the difference of zinc uptake efficiency of zinc-aspartate complex (Zn-Asp) into various organs compared with $ZnSO_4$. We observed that Plasma zinc concentration in both $ZnSO_4$ and Zn-Asp administrated group was increased progressively following administration, and reached a peak level at 2 hr. The increasing pattern of zinc concentration was similar to each groups, however the zinc concentration of Zn-Asp administrated group was higher than that of $ZnSO_4$ administrated group. We found that prostatic zinc level of Zn-Asp administrated group was higher than $ZnSO_4$ administrated group, and was increased approximately $\sim$2.7 fold and $\sim$4.2 fold at 4 and 8 hr after administration. From these observations, we suggest than Zn-Asp has high uptake efficiency of zinc into the prostate gland. Therefore, Zn-Asp is potentially useful treatment of many prostatic diseases.

• Environmental Analysis Health and Toxicology
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• v.19 no.2
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• pp.191-200
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• 2004

Zinc (Zn) is an essential element in biological process, however inadequate Zn status in general population have been recognized. To update the knowledge for Zn-cadmium (Cd) interaction, we studied the intestinal uptake and transport, and the expression of metal transporter proteins (divalent metal transporter 1, DMT1 ; metal transporter protein 1, MTP1 ; zinc transporter 1, ZnTl ; metallothionein 1 , MT1) in duodenum after Cd exposure using Zn deficient animal model. Rats were led Zn deficient (ZnD, 0.5-1.0 mgZn/kg) or Zn supplemented (ZnS, 50mg Zn/kg) diet for 4 weeks, and followed single administration of $^{109}$ CdCl$_2$orally. The body Zn flatus and tissue Cd concentration were determined at 24 hrs after Cd administration. Total body burden of Cd and Cd absorption index (AI, %) were estimated based on the tissue Cd analyzed. DMT1, MTP1, ZnTl and MT1 mRNA were analyzed by using RT-PCR method. Feeding of Zn deficient diet for 4 weeks produced a reduced body weight gain and a depletion of body Zn. Tissue Cd concentration, body burden of Cd and Cd absorption index were higher in the ZnD diet fed rats than the ZnS diet red rats. Especially, Cd concentration in the small intestine (duodenum, jejunum and ileum) and the colon of FeD diet fed rats were higher markedly than in the FeS diet group. The expression levels of DMT1, MTP1 and ZnT1 mRNA in FeD diet fed rats were similar to the FeS diet. The level of MT1 mRNA expression was significantly lower in the FeD than the FeS diet fed rats. Taken together, theses results indicate that Zn deficiency in diet induce an increased intestinal absorption and tissue retention of Cd, and down -regulate the MT1 expression in the intestine which might be play a part of role in Cd absorption and transport in mammalian. These findings suggest that deficiency of essential metal could be enhanced the toxicity of toxic, non-esstial metals through the metal-metal interaction.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3355-3360
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• 2015

Background: Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status. Materials and Methods: IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transporter genes and the grade of glioma, as well as IDH1 mutation status, were investigated. Results: Among the four zinc transporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade (grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p<0.0001). However, only ZIP11 exhibited weak correlation with IDH1 mutation status (p=0.045). Samples with mutations in IDH1 displayed higher ZIP11 expression than those without IDH1 mutations. Conclusions: This finding indicated that zinc transporters may interact with IDH1 mutation by direct modulation or action in some shared pathways or genes to promote the development of glioma. Zinc transporters may play an important role in glioma. ZIP4 and ZIP11 are promising molecular diagnostic markers and novel therapeutic targets. Nevertheless, the detailed biological function of zinc transporters and the mechanism of the potential interaction between ZIP11 and IDH1 mutation in gliomagenesis should be further investigated.

• Applied Microscopy
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• v.32 no.4
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• pp.377-383
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• 2002

We have detected the murine zinc transporter, ZnT3, and zinc ions in the mouse choroid plexus by immunocytochemistry (ICC) and zinc selenium autometallography ($ZnSe^{AMG}$), respectively. BALB/c mice served as experimental animals. Routine floating ABC immunocytochemical procedures were used for the ZnT3 immunocytochemistry, and the mice were injected intraperitoneally (i.p.) with sodium selenide (10 mg/kg) for the zinc selenium autometallography. The choroid plexus showed weak immunoreactivity (Ir) for ZnT3. At high magnification, ZnT3-Ir was seen to be located in the choroid epithelium and the connective tissue of the capillaries. At the EM level, a high electron density of ZnT3-immunoreactivity was restricted to vesicle membranes as well as microvilli in the apical membrane. In contrast, immunostaining of ZnT3 was completely absent in the basolateral plasma membrane and other cell organelles. After silver enhancement, fine $ZnSe^{AMG}$ grains were observed in both the epithelial and endothelial cells of the choroid plexus. Few $ZnSe^{AMG}$ grains present in the cell bodies of the choroid epithelial cells were located in multivesicular bodies. It is striking that very many $ZnSe^{AMG}$ grains were observed in the endothelial cells of the capillaries. These findings establish the choroid plexus as a non-neuronal pool of zinc ions in the brain, although the functional significance of this pool is not clear. The choroid epithelium, however, may play an important role in the transportation of zinc between the CSF and brain tissue.

• Applied Microscopy
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• v.38 no.1
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• pp.29-34
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• 2008

Small amounts of zinc ions regulate a plentitude of enzymatic proteins, receptors and transcription factors, thus cells need accurate homeostasis of zinc ions. Some neurons have developed mechanisms to accumulate zinc in specific membrane compartment ("vesicular zinc"), which can be evidenced using histochemical techniques. These neurons are the socalled zinc enriched (ZEN) neurons, which accumulate glutamate and zinc inside their synaptic vesicles and release it during synaptic transmission. In the present paper we have studied the distribution of the ZEN terminals in the rat hippo-campus using ZnSe autometallography, Neo-Timm staining, ZnT3 immunohistochemistry and TSQ fluorescence staining.

• Journal of Nutrition and Health
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• v.51 no.6
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• pp.489-497
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• 2018

Purpose: Obesity is often associated with disturbances in the mineral metabolism. The purpose of this study was to investigate the effects of high-fat diet-induced obesity on tissue zinc concentrations and zinc transporter expressions in mice. Methods: C57BL/6J male mice were fed either a control diet (10% energy from fat, control group) or a high-fat diet (45% energy from fat, obese group) for 15 weeks. The zinc concentrations in the serum, stool, and various tissues were measured by inductively coupled plasma (ICP)-atomic emission spectrophotometry or ICP-mass spectrophotometry. The levels of zinc transporter mRNAs in the liver, duodenum, and pancreas were measured by real-time RT-PCR. The levels of serum adipokines, such as leptin and IL-6, were determined. Results: The total body weight, adipose tissue weight, and hepatic TG and cholesterol concentrations were significantly higher in the obese group, as compared to the control group. The obese group had significantly higher levels of serum leptin and pro-inflammatory IL-6 concentrations, and had significantly lower levels of serum alkaline phosphatase activity. The zinc concentrations of the liver, kidney, duodenum, and pancreas were all significantly lower in the obese group than in the control group. On the other hand, the fecal zinc concentrations were significantly higher in the obese group than in the control group. The serum zinc concentrations were not significantly different between the two groups. The ZnT1 mRNA levels of the liver and the pancreas were significantly higher in the obese group, as compared to the control group. Hepatic Zip10 mRNA was also increased in the obese group. Conclusion: Our study findings suggest that obesity increases fecal zinc excretion and lowers the tissue zinc concentrations, which may be associated with alterations in the zinc transporter expressions.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.8
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• pp.1189-1196
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• 2013

Adipose tissue development and function play a critical role in the regulation of energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes. Although the effect of zinc ascorbate supplementation in diabetes or glycemic control is known in humans, the underlying mechanism is not well described. Here, we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d significantly promoted adipogenesis, which was characterized by increased glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed that ZnC increased the sequential expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha (C/$EBP{\alpha}$), the key transcription factors of adipogenesis. These results indicate that ZnC could promote adipogenesis through $PPAR{\gamma}$ and C/$EBP{\alpha}$, which act synergistically for the expression of aP2 and GLUT4, leading to the generation of insulin-responsive adipocytes and can thereby be useful as a novel therapeutic agent for the management of diabetes and related metabolic disorders.

• Environmental Analysis Health and Toxicology
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• v.19 no.4
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• pp.389-399
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• 2004

Metallothionein (MT), a small protein molecule which can bind or release metal ions, is involved in the regulation of cellular metal homeostasis. This study was investigated the accumulation of cadmium in blood, tissue (liver, kidney and brain), and the effect of cadmium on several key genes (MT-I, MT-II, ZnT-1) in zinc metabolism in the mouse. Mouses weighing 20∼25 g were randomly assigned to control and cadmium treated group (Cd group). Cd group was intraperitoneally injected with cadmium 2, 4, 8 mg/kg and control group was administerd with saline. Mouses of each group were sacrificed by decapitation 4 hours after the administration of cadmium. Cadmium contents in blood, liver, kidney and brain were increased by a dose-dependent manner. Accumulation of cadmium was mainly occurred in liver and kidney. Induction of MT-I and MT-II protein was increased, but ZnT-1 expression was decreased in a dose-dependent manner by the treatment of 2∼8 mg/kg cadmium. These results suggested that cadmium can be transported to brain and alter the expression of several key genes in zinc homeostasis.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.248-254
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• 2022

Background: Zinc homeostasis is essential for human health and is regulated by several zinc transporters including ZIP and ZnT. ZIP4 is expressed in the small intestine and is important for zinc absorption from the diet. We investigated in the present study the effects of Panax ginseng (P. ginseng) extract on modulating Zip4 expression and cellular zinc levels in mouse Hepa cells. Methods: Hepa cells were transfected with a luciferase reporter plasmid that contains metal-responsive elements, incubated with P. ginseng extract, and luciferase activity was measured. Using ⁶⁵ZnCl₂, zinc uptake in P. ginseng-treated cells was measured. The expression of Zip4 mRNA and protein in Hepa cells was also investigated. Finally, using a luciferase reporter assay system, the effects of several ginsenosides were monitored. Results: The luciferase activity in cells incubated with P. ginseng extract was significantly higher than that of control cells cultured in normal medium. Hepa cells treated with P. ginseng extract exhibited higher zinc uptake. P. ginseng extract induced Zip4 mRNA expression, which resulted in an enhancement of Zip4 protein expression. Furthermore, some ginsenosides, such as ginsenoside Rc and Re, enhanced luciferase activity driven by intracellular zinc levels. Conclusion: P. ginseng extract induced Zip4 expression at the mRNA and protein level and resulted in higher zinc uptake in Hepa cells. Some ginsenosides facilitated zinc influx. On the basis of these results, we suggest a novel effect of P. ginseng on Zip4-mediated zinc influx, which may provide a new strategy for preventing zinc deficiency.