• Molecular & Cellular Toxicology
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• 제3권4호
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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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• 제3권2호
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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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• 제19권2호
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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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• 제16권8호
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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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• 제32권4호
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• pp.377-383
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• 2002

본 연구는 BALB/c 생쥐 맥악얼기내 ZnT3 및 zinc 이온을 ZnT3 항혈청을 이용한 면역세포화학법(ABC법)과 autometallography ($ZnSe^{AMG}$)로 각각 동정하였다. 저배율에서 맥락얼기내 ZnT3 면역반응은 미약하였으나, 고배율에서는 맥락상피와 맥락조직에 국한된 뚜렷한 면역반응이 관찰되었다. 전자현미경에서 관찰된 ZnT3 면역반응은 주로 맥락상피의 자유면쪽 미세융모 및 막성 소기관에 국한되었던 반면 맥락조직내 모세혈관의 내피세포에서는 면역반응이 전혀 관찰되지 않았다. AMG 염색결과 맥락상피와 맥락조직에서 강한 AMG 과립이 관찰되었으며, 특히 모세혈관의 내피상피에서 가장 많이 AMG 과립이 분포하고 있었다. 맥락상피내 AMG 과립은 주로 다소포체에서 관찰되었으며, 소수는 특정 세포질소기관과 상관없이 사이토졸에 산재해 있었다. 이러한 본 연구의 결과를 바탕으로 저자들은 맥락얼기가 일종의 zinc pool의 역할이 있을 것이며, 최소한 뇌척수액과 뇌실질간에 zinc의 이동에 중요한 역할을 담당할 것으로 믿는다.

• Applied Microscopy
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• 제38권1호
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• pp.29-34
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• 2008

본 연구자는 Zinc Selenium autometallography ($ZnSe^{AMG}$) (Danscher et al., 1997) 염색법을 중심으로 중추신경계통 내 zinc ($Zn^{2+}$)의 분포와 이들을 함유하고 있는 신경종말, 소위 ZEN(zinc-enriched) terminals의 미세구조에 관하여 보고한 바 있다. 이번 연구에서는 다른 몇 가지, 즉 Neo-Timm staining (Danscher, 1982), TSQ fluorescence staining (Frederickson et al.,1987), Zinc transporter-3 Immunohistochemistry ($ZnT3^{IHC}$) (Palmiter et at., 1997) 염색법으로 흰쥐 해마복합체에 분포하는 $Zn^{2+}$를 염색한 후 이들의 염색패턴에서 차이점을 밝히고자 하였다. $ZnSe^{AMG}$ 염색법은 $Zn^{2+}$에 대한 특이성은 다소 떨어지나 광학 및 전자현미경하에서 관찰이 가능하며, 반영구적인 표본으로 보관이 가능하다는 장점이 있었고, TSQ는 $Zn^{2+}$에 대한 특이성이 매우 높을 뿐 아니라 그 염색법이 매우 간단하다는 장점이 있는 반면 형광물질의 안정성과 표본보관이 용이하지 않다는 단점이 있다. 그 외 Neo-Timm 염색법은 TSQ형광염색법과 유사한 염색 패턴을 보였으며, $ZnT3^{IHC}$염색법은 오히려 $ZnSe^{AMG}$에 가까운 염색의 결과를 보였다. 본 연구의 결과는 중추신경계통 내 $Zn^{2+}$에 관한 형태학적 연구에서 기초자료로 활용될 수 있을 것이다.

• Journal of Nutrition and Health
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• 제51권6호
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• pp.489-497
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• 2018

본 연구에서는 고지방식이로 유도한 비만군과 저지방식이를 공급한 대조군에서 각 조직의 아연 농도와 아연수송체 발현 수준을 비교하여, 비만 상태가 아연 대사에 미치는 영향을 파악하고자 하였다. C57BL/6J mice를 두 군으로 나누어 각 군당 15마리씩 고지방식이 (비만군) 또는 저지방식이 (대조군)를 총 15주간 공급하였다. 본 연구 결과, 비만군은 대조군에 비해 체중 증가량, 부위별 지방조직, 혈청과 간의 중성지방과 콜레스테롤 농도, 혈청 ALT 및 AST 활성 등이 모두 유의적으로 높게 나타났다. 또한 혈청 렙틴과 염증성 사이토카인인 IL-6의 농도도 비만군에서 유의적으로 증가하였다. 조직 별 아연 농도를 비교한 결과, 간, 소장, 신장, 췌장 등의 측정한 모든 조직에서 비만군이 대조군에 비해 유의적으로 낮게 나타났으며, 대변으로 배설되는 아연 함량은 비만군이 대조군에 비해 유의적으로 높았다. 혈청 아연 농도의 경우 두 군 간 유의적인 차이가 없었으나, 혈청 내 아연-의존 금속효소인 ALP 활성은 비만군에서 대조군에 비해 유의적으로 낮게 나타나 아연의 기능적인 결핍을 확인하였다. 내인성 아연의 체외 배출에 관여하는 췌장 조직에서의 ZnT1 mRNA 수준은 비만군에서 대조군에 비해 유의적으로 높게 나타났으며, 식이 아연 흡수에 관여하는 소장에서의 Zip4와 ZnT1의 mRNA 수준은 두 군간에 유의적인 차이가 없었다. 간 조직의 경우, ZnT1과 Zip10 mRNA이 모두 비만군에서 유의적으로 증가하였다. 이상의 결과를 요약하면, 비만 상태는 아연의 배설 증가와 조직 내 아연 농도 감소를 유발하는 것으로 나타났으며, 이들 아연 대사의 변화는 췌장과 간 조직의 아연 수송체 발현 수준 변화와 밀접한 관련이 있는 것으로 보인다. 비만인들에서 아연 영양상태가 결핍되지 않도록 관심을 가져야 할 것으로 생각되며, 비만으로 인한 아연 대사의 이상 (dysfunction)을 억제하기 위해서는 아연 수송체 발현을 조절할 수 있는 요인들에 대한 이해가 더욱 필요할 것으로 생각된다.

• Asian-Australasian Journal of Animal Sciences
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• 제26권8호
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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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• 제19권4호
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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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• 제46권2호
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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.