• Toxicological Research
• /
• 제23권1호
• /
• pp.1-9
• /
• 2007

Transporters are membrane proteins that mediate the transfer of substrate across the cellular membrane. In this overview, the characteristics and the toxicological relevance were discussed for various types of transporters. For drug transporters, the overview focused on ATP-binding cassette transporters and solute carrier family 21A/22A member transporters. Except for OCTN transporters and OATP transporters, drug transporters tend to have broad substrate specificity, suggesting drug-drug interaction at the level of transport processes (e.g., interaction between methotrexate and non-steroidal anti-inflammatory agents) is likely. For metal transporters, transporters for zinc, copper and multiple metals were discussed in this overview. These metal transporters have comparatively narrow substrate specificity, except for multiple metal transporters, suggesting that inter-substrate interaction at the level of transport is less likely. In contrast, the expressions of the transporters are often regulated by their substrates, suggesting cellular adaptation mechanism exists for these transporters. The drug-drug interactions in drug transporters and the cellular adaptation mechanisms for metal transporters are likely to lead to alterations in pharmacokinetics and cellular metal homeostasis, which may be linked to the development of toxicity. Therefore, the transporter-mediated alterations may have toxicological relevance.

• Molecules and Cells
• /
• 제44권5호
• /
• pp.335-341
• /
• 2021

Zinc is an essential micronutrient with crucial roles in multiple facets of biological processes. Dysregulated zinc homeostasis impairs overall immune function and resultantly increases susceptibility to infection. Clinically, zinc supplementation is practiced for treatment of several infectious diseases, such as diarrhea and malaria. Recent focus on zinc as a beneficial element for immune system support has resulted in investigation of the immunomodulatory roles of zinc in a variety of immune cells. Besides its classical role as a cofactor that regulates the structural function of thousands of proteins, accumulating evidence suggests that zinc also acts, in a manner similar to calcium, as an ionic regulator of immune responses via participation as an intracellular messenger in signaling pathways. In this review, we focus on the role of zinc as a signaling molecule in major pathways such as those downstream of Toll-like receptors-, T cell receptor-, and cytokine-mediated signal transduction that regulate the activity and function of monocytes/macrophages and T cells, principal players in the innate and adaptive immune systems.

• 미생물학회지
• /
• 제47권4호
• /
• pp.281-288
• /
• 2011

스트레스 반응에 관여하는 Saccharomyces cerevisiae 전사인자인 Msn2/4의 $C_2H_2$ zinc finger 부위와 아미노산 서열 유사성을 보이는 Aspergillus nidulans MsnA의 하위 유전자 획득을 위하여 msnA 결손 돌연변이체 또는 과발현 균주에서 야생주와 비교하여 차별적으로 발현되는 유전자(Differentially Expressed Gene, DEG)들을 분리하였다. 선별된 DEG들은 염기서열 결정을 통해 해당 유전자들을 동정하였고 이들 중 DEG6는 단당류 수송자(monosaccharide transporter)로 예측된 mstB 유전자로 밝혀졌다. mstB의 발현은 MsnA 과발현에 의하여 증가되었으며 MsnA는 in vitro에서 mstB 프로모터 부위에 직접적으로 결합하였다. MstB는 12개의 막결합 부위를 가지며 A. niger의 고친화성 단당류 수송자(high-affinity monosaccharide transporter)인 MstA와 80%의 높은 아미노산 서열 동일성을 보였다. mstB 결손 돌연변이체의 표현형은 야생주와 유사하였으나 MstB가 과발현된 균주는 낮은 당 농도인 0.1% glucose 배지에서 유성생식 기관인 cleistothecia의 형성이 증가하였다. 이러한 결과는 단당류 수송자인 MstB가 유성분화 과정에서 요구되는 당의 수송에 관여하고 있음을 시사한다.

• Journal of Ginseng Research
• /
• 제46권2호
• /
• pp.248-254
• /
• 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.

• Environmental Analysis Health and Toxicology
• /
• 제19권4호
• /
• pp.389-399
• /
• 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.

• Toxicological Research
• /
• 제35권4호
• /
• pp.311-317
• /
• 2019

The transport systems for metals play crucial roles in both the physiological functions of essential metals and the toxic effects of hazardous metals in mammals and plants. In mammalian cells, Zn transporters such as ZIP8 and ZIP14 have been found to function as the transporters for Mn(II) and Cd(II), contributing to the maintenance of Mn homeostasis and metallothionein-independent transports of Cd, respectively. In rice, the Mn transporter OsNramp5 expressed in the root is used for the uptake of Cd from the soil. Japan began to cultivate OsNramp5 mutant rice, which was found to accumulate little Cd, to prevent Cd accumulation. Inorganic trivalent arsenic (As(III)) is absorbed into mammalian cells via aquaglyceroporin, a water and glycerol channel. The ortholog of aquaporin in rice, OsLsi1, was found to be an Si transporter expressed in rice root, and is responsible for the absorption of soil As(III) into the root. Since rice is a hyperaccumulator of Si, higher amounts of As(III) are incorporated into rice compared to other plants. Thus, the transporters of essential metals are also utilized to incorporate toxic metals in both mammals and plants, and understanding the mechanisms of metal transports is important for the development of mitigation strategies against food contamination.

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

• Applied Microscopy
• /
• 제32권4호
• /
• pp.377-383
• /
• 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.

• Journal of Animal Science and Technology
• /
• 제64권6호
• /
• pp.1092-1104
• /
• 2022

Using antibiotics as growth promoter has been banned in poultry feed industry, thus various researchers try to seek an alternative to replace the growth-promoting antibiotics. In this study, we aimed to evaluate the growth performance via intestinal nutrient utilization and cecal microbial composition of broiler after dietary supplementation with most commonly using antibiotics, zinc bacitracin, and sophorolipid. A total of 180 1-day-old chicks were randomly assigned, and dietary treatment was as follow: CON, basal diet; ZB, 100 ppm of zinc bacitracin supplemented diet; and SPL, 250 ppm of sophorolipid supplemented diet. Their growth performance was evaluated and the samples of blood, small intestine, and ileal and cecal digesta were collected for biochemical, histological, and genomic analyses. The body weight and average daily gain of 7-day-old chicks were higher in ZB and those in overall experimental period were improved by ZB and SPL supplementation (p < 0.05). Their intestinal characteristics were not affected by dietary treatments in duodenum and ileum. Nonetheless, villus height was increased by SPL supplementation in jejunum (p < 0.05). Moreover, dietary SPL supplementation could down-regulate the expression level of pro-inflammatory cytokine, IL-1β (p < 0.05). mRNA levels of lipid and protein transporters did not differ among the treatments, however, relative expression levels of carbohydrate transporters, GLUT2 and SGLT1 were increased in broiler chicken's jejumum fed zinc bacitracin and sophorolipid supplemented diets (p < 0.05). Dietary zinc bacitracin supplementation could increase the population of Firmicutes in phylum level, and the portion of Turiciacter in genus level. On the other hands, the portion of Faecalibacterium was increased by dietary SPL supplementation compared to the other treatments. Our findings suggest that SPL supplementation improves growth performance through enhanced carbohydrate utilization capacity via improvement of gut morphological status and modulation of the cecal microbial population of broilers.

• Asian-Australasian Journal of Animal Sciences
• /
• 제26권8호
• /
• pp.1189-1196
• /
• 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.