• Title/Summary/Keyword: transporters

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Expression Profile Analysis of Zinc Transporters (ZIP4, ZIP9, ZIP11, ZnT9) in Gliomas and their Correlation with IDH1 Mutation Status

  • Kang, Xing;Chen, Rong;Zhang, Jie;Li, Gang;Dai, Peng-Gao;Chen, Chao;Wang, Hui-Juan
    • 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.

Development of Optimal Planning System for Operating Transporters in Shipyard (조선소 트랜스포터 운영을 위한 최적 계획 시스템 개발)

  • Cha, Ju-Hwan;Cho, Doo-Yeoun;Ruy, Won-Sun;Hwang, Ho-Jin
    • Korean Journal of Computational Design and Engineering
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    • v.21 no.2
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    • pp.177-185
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    • 2016
  • In this paper, an optimal planning system for operating transporters in shipyard is developed. The system is designed to utilize the geometries of shipyard, and manage the data of blocks and transporters directly. There are four major menus such as shipyard map management based on GIS, block transportation request, transporter management, and optimal transportation planning in the system. The geometries and properties of the shops, roads, and addresses are manipulated in the shipyard map management menu. The block transportation requests and the properties of transporters are managed in the block transportation request and transporter management menus, respectively. The optimum transportation is planned automatically for minimizing the unload times of the transporters, and the optimum transportation plans are confirmed and printed to the transporter drivers. The effectiveness of the system was verified through the application to a large-sized shipyard.

Sympathetic and parasympathetic regulation of sodium transporters and water channels in rat submandibular gland

  • Jung, Hyun;Ryu, Sun-Youl
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.1
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    • pp.1-7
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    • 2006
  • The present study was aimed to explore the role of sympathetic and parasympathetic nerves in the regulation of sodium transporters and water channels in the salivary gland. Rats were denervated of their sympathetic and parasympathetic nerves to the submandibular gland, and the glandular expression of sodium transporters and water channels was determined by Western blot analysis. The expression of either ${\alpha}1$ or ${\beta}1$ subunit of Na, K-ATPase was not significantly affected either by the sympathetic or by the parasympathetic denervation. The expression of subunits of epithelial sodium channels was significantly increased both in the denervated and contralateral glands either by the sympathetic or by the parasympathetic denervation. Neither the sympathetic nor the parasympathetic denervation significantly altered the expression of aquaporin-1 (AQP1). Nor was the expression of AQP4 affected significantly by the parasympathetic or the sympathetic denervation. On the contrary, the expression of AQP5 was significantly increased not only by the parasympathetic but also by the sympathetic denervation. These results suggest that sympathetic and parasympathetic nerves have tonic regulatory effects on the regulation of certain sodium transporters and AQP water channels in the salivary gland.

Targeting Multidrug Resistance with Small Molecules for Cancer Therapy

  • Xia, Yan;Lee, Kyeong
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.375-385
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    • 2010
  • Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting multidrug resistance (MDR), which is caused by changes in the levels or activity of membrane transporters that mediate energy-dependent drug efflux and of proteins that affect drug metabolism and/or drug action. Cancer scientists and oncologists have worked together for some time to understand anticancer drug resistance and develop pharmacological strategies to overcome such resistance. Much focus has been on the reversal of the MDR phenotype by inhibition of ATP-binding cassette (ABC) drug transporters. ABC transporters are a family of transporter proteins that mediate drug resistance and low drug bioavailability by pumping various drugs out of cells at the expense of ATP hydrolysis. Many inhibitors of MDR transporters have been identified, and though some are currently undergoing clinical trials, none are in clinical use. Herein, we briefly review the status of MDR in human cancer, explore the pathways of MDR in chemotherapy, and outline recent advances in the design and development of MDR modulators.

Sodium/chloride-Dependent Transporters: Elucidation of Their Properties Using the Dopamine Transporter

  • Caron, Marc G.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.88-93
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    • 1994
  • The mechanisms controlling the intensity and duration of synaptic transmission are numerous. Once an action potential reaches a nerve terminal, the stored neurotransmitters are released in a quantum fashion into the synaptic cleft. At that point neurotransmitters can act on post-synaptic receptors to elicit an action on the post-synaptic cell or net at so-called auto-receptors that are located on the presynaptic side and which often regulate the further release of the neutotransmitter. Whereas the action of the neurotransmitter receptors is regulated by desensitization phenomenon, the major mechanism by which the intensity and duration of neurotransmitter action is presumably regulated by either its degradation or its removal from the synaptic cleft. In the central nervous system, specialized proteins located in fe plasma membrane of presynaptic terminals function to rapidly remove neurotransmitters from the synaptic cleft in a sodium chloride-dependent fashion. These proteins have been referred to as uptake sites or neurotransmitter transporters. Once taken up by the plasma membrane transporters, neurotransmitters are repackaged into secretory vesicles by distinct transporters which depend on a proton gradient.

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Cross-reactivity of Human Polyclonal Anti-GLUT1 Antisera with the Endogenous Insect Cell Glucose Transporters and the Baculovirus-expressed GLUT1

  • Lee, Chong-Kee
    • Biomedical Science Letters
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    • v.7 no.4
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    • pp.161-166
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    • 2001
  • Most mammalian cells take up glucose by passive transport proteins in the plasma membranes. The best known of these proteins is the human erythrocyte glucose transporter, GLUT1. High levels of heterologous expression far the transporter are necessary for the investigation of its three-dimensional structure by crystallization. To achieve this, the baculovirus expression system has become popular choice. However, Spodoptera frugiperda Clone 9 (Sf9) cells, which are commonly employed as the host permissive cell line to support baculovirus replication and protein synthesis, grow well on TC-100 medium that contains 0.1% D-glucose as the major carbon source, suggesting the presence of endogenous glucose transporters. Furthermore, very little is known of the endogenous transporters properties of Sf9 cells. Therefore, human GLUT1 antibodies would play an important role for characterization of the GLUT1 expressed in insect cell. However, the successful use of such antibodies for characterization of GLUT1 expression m insect cells relies upon their specificity for the human protein and lack of cross-reaction with endogenous transporters. It is therefore important to determine the potential cross-reactivity of the antibodies with the endogenous insect cell glucose transporters. In the present study, the potential cross-reactivity of the human GLUT1 antibodies with the endogenous insect cell glucose transporters was examined by Western blotting. Neither the antibodies against intact GLUT1 nor those against the C-terminus labelled any band migrating in the region expected fur a protein of M$_r$ comparable to GLUT1, whereas these antibodies specifically recognized the human GLUT1. Specificity of the human GLUT1 antibodies tested was also shown by cross-reaction with the GLUT1 expressed in insect cells. In addition, the insect cell glucose transporter was found to have very low affinity for cytochalasin B, a potent inhibitor of human erythrocyte glucose transporter.

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Tryptophan-Based Hyperproduction of Bioindigo by Combinatorial Overexpression of Two Different Tryptophan Transporters

  • Hyun Jin Kim;Sion Ham;Nara-Shin;Jeong Hyeon Hwang;Suk Jin Oh;Tae-Rim Choi;Jeong Chan Joo;Shashi Kant Bhatia;Yung-Hun Yang
    • Journal of Microbiology and Biotechnology
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    • v.34 no.4
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    • pp.969-977
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    • 2024
  • Indigo is a valuable, natural blue dye that has been used for centuries in the textile industry. The large-scale commercial production of indigo relies on its extraction from plants and chemical synthesis. Studies are being conducted to develop methods for environment-friendly and sustainable production of indigo using genetically engineered microbes. Here, to enhance the yield of bioindigo from an E. coli whole-cell system containing tryptophanase (TnaA) and flavin-containing monooxygenase (FMO), we evaluated tryptophan transporters to improve the transport of aromatic compounds, such as indole and tryptophan, which are not easily soluble and passable through cell walls. Among the three transporters, Mtr, AroP, and TnaB, AroP enhanced indigo production the most. The combination of each transporter with AroP was also evaluated, and the combination of AroP and TnaB showed the best performance compared to the single transporters and two transporters. Bioindigo production was then optimized by examining the culture medium, temperature, isopropyl β-D-1-thiogalactopyranoside concentration, shaking speed (rpm), and pH. The novel strain containing aroP and tnaB plasmid with tnaA and FMO produced 8.77 mM (2.3 g/l) of bioindigo after 66 h of culture. The produced bioindigo was further recovered using a simple method and used as a watercolor dye, showing good mixing with other colors and color retention for a relatively long time. This study presents an effective strategy for enhancing indigo production using a combination of transporters.

Expression and regulation of prostaglandin transporters, ATP-binding cassette, subfamily C, member 1 and 9, and solute carrier organic anion transporter family, member 2A1 and 5A1 in the uterine endometrium during the estrous cycle and pregnancy in pigs

  • Jang, Hwanhee;Choi, Yohan;Yoo, Inkyu;Han, Jisoo;Kim, Minjeong;Ka, Hakhyun
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.5
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    • pp.643-652
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    • 2017
  • Objective: Prostaglandins (PGs) function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ATP-binding cassette, subfamily C, member 4 (ABCC4) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1) are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta. Methods: Uterine endometrial tissues were obtained from gilts on day (D) 12 and D15 of the estrous cycle and days 12, 15, 30, 60, 90, and 114 of pregnancy. Results: ABCC1, ABCC9, SLCO4C1, and SLCO5A1 mRNAs were expressed in the uterine endometrium, and levels of expression changed during the estrous cycle and pregnancy. Expression of ABCC1 and ABCC9 mRNAs was localized mainly to luminal and glandular epithelial cells in the uterine endometrium, and chorionic epithelial cells during pregnancy. Conceptuses during early pregnancy and chorioallantoic tissues from mid to late pregnancy also expressed these PG transporters. $Estradiol-17{\beta}$ increased the expression of ABCC1 and SLCO5A1, but not ABCC9 and SLCO4C1 mRNAs and increasing doses of $interleukin-1{\beta}$ induced the expression of ABCC9, SLCO4C1, and SLCO5A1 mRNAs in endometrial explant tissues. Conclusion: These data showed that several PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 were expressed at the maternal-conceptus interface, suggesting that these PG transporters may play an important role in the establishment and maintenance of pregnancy by regulating PG transport in the uterine endometrium and placenta in pigs.

Involvement of NRF2 Signaling in Doxorubicin Resistance of Cancer Stem Cell-Enriched Colonospheres

  • Ryoo, In-geun;Kim, Geon;Choi, Bo-hyun;Lee, Sang-hwan;Kwak, Mi-Kyoung
    • Biomolecules & Therapeutics
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    • v.24 no.5
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    • pp.482-488
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    • 2016
  • Cancer stem cells (CSCs) are a subset of tumor cells, which are characterized by resistance against chemotherapy and environmental stress, and are known to cause tumor relapse after therapy. A number of molecular mechanisms underlie the chemoresistance of CSCs, including high expression levels of drug efflux transporters. We investigated the role of the antioxidant transcription factor NF-E2-related factor 2 (NRF2) in chemoresistance development, using a CSC-enriched colonosphere system. HCT116 colonospheres were more resistant to doxorubicin-induced cell death and expressed higher levels of drug efflux transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) compared to HCT116 monolayers. Notably, levels of NRF2 and expression of its target genes were substantially elevated in colonospheres, and these increases were linked to doxorubicin resistance. When NRF2 expression was silenced in colonospheres, Pgp and BCRP expression was downregulated, and doxorubicin resistance was diminished. Collectively, these results indicate that NRF2 activation contributes to chemoresistance acquisition in CSC-enriched colonospheres through the upregulation of drug efflux transporters.