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Your search keyword '"Concentrative nucleoside transporter"' showing total 8 results
Start Over Descriptor "Concentrative nucleoside transporter" Publisher elsevier
8 results on '"Concentrative nucleoside transporter"'

1. Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters

Author

Yamamura, Taiki, Narumi, Katsuya, Ohata, Tsukika, Satoh, Hiroshi, Mori, Takao, Furugen, Ayako, Kobayashi, Masaki, Iseki, Ken, Yamamura, Taiki, Narumi, Katsuya, Ohata, Tsukika, Satoh, Hiroshi, Mori, Takao, Furugen, Ayako, Kobayashi, Masaki, and Iseki, Ken

Abstract

Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize CNT-subtype specificity to understand the systemic disposition of deoxyribonucleosides (dNs) and their analogs, the involvement of CNTs in transporting dNs is not fully understood. In this study, using COS-7 cells that transiently expressed CNT1, CNT2, or CNT3, we investigated if CNTs could transport not only ribonucleosides but also dNs, i.e., 2'-deoxyadenosine (dAdo), 2'-deoxyguanosine (dGuo), and 2'-deoxycytidine (dCyd). The cellular uptake study demonstrated that dAdo and dGuo were taken up by CNT2 but not by CNT1. Although dCyd was taken up by CNT1, no significant uptake was detected in COS-7 cells expressing CNT2. Similarly, these dNs were transported by CNT3. The apparent K-m values of their uptake were as follows: CNT1, K-m = 141 mu M for dCyd; CNT2, K-m = 62.4 mM and 54.9 mu M for dAdo and dGuo, respectively; CNT3, K-m = 14.7 mM and 34.4 mu M for dGuo and dCyd, respectively. These results demonstrate that CNTs contribute not only to ribonucleoside transport but also to the transport of dNs. Moreover, our data indicated that CNT1 and CNT2 selectively transported pyrimidine and purine dNs, respectively, and CNT3 was shown to transport both pyrimidine and purine dNs.

Published
2021

2. Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters.

Author

Yamamura T, Narumi K, Ohata T, Satoh H, Mori T, Furugen A, Kobayashi M, and Iseki K

Subjects
Animals, Biological Transport, Active, COS Cells, Chlorocebus aethiops, Deoxyadenosines metabolism, Deoxycytidine metabolism, Deoxyguanosine metabolism, Humans, Kinetics, Membrane Transport Proteins genetics, Recombinant Proteins genetics, Recombinant Proteins metabolism, Deoxyribonucleosides metabolism, Membrane Transport Proteins metabolism
Abstract

Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize CNT-subtype specificity to understand the systemic disposition of deoxyribonucleosides (dNs) and their analogs, the involvement of CNTs in transporting dNs is not fully understood. In this study, using COS-7 cells that transiently expressed CNT1, CNT2, or CNT3, we investigated if CNTs could transport not only ribonucleosides but also dNs, i.e., 2'-deoxyadenosine (dAdo), 2'-deoxyguanosine (dGuo), and 2'-deoxycytidine (dCyd). The cellular uptake study demonstrated that dAdo and dGuo were taken up by CNT2 but not by CNT1. Although dCyd was taken up by CNT1, no significant uptake was detected in COS-7 cells expressing CNT2. Similarly, these dNs were transported by CNT3. The apparent K m values of their uptake were as follows: CNT1, K m ＝ 141 μM for dCyd; CNT2, K m ＝ 62.4 μM and 54.9 μM for dAdo and dGuo, respectively; CNT3, K m ＝ 14.7 μM and 34.4 μM for dGuo and dCyd, respectively. These results demonstrate that CNTs contribute not only to ribonucleoside transport but also to the transport of dNs. Moreover, our data indicated that CNT1 and CNT2 selectively transported pyrimidine and purine dNs, respectively, and CNT3 was shown to transport both pyrimidine and purine dNs., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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3. Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells

Author

Johannes Matthias Löhr, Ralf Jesnowski, and Wolfgang Hagmann

Subjects
Cancer Research, HEK 293 cells, Equilibrative nucleoside transporter, Pharmacology, Biology, ABCC5, medicine.disease, Equilibrative nucleoside transporter 1, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Gemcitabine, Concentrative nucleoside transporter, Cell culture, Pancreatic cancer, medicine, biology.protein, medicine.drug
Abstract

Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU) alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5) influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days) did not alter the messenger RNA (mRNA) expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1), whereas high dosages of the drug (20 µM for 1 hour) elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine), the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1) or MRP5-silenced (PANC1/shMRP5) cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

Published
2010

4. Liposome Reconstitution and Transport Assay for Recombinant Transporters

Author

Seok-Yong Lee and Zachary Lee Johnson

Subjects
Liposome, Transporter, Biology, medicine.disease_cause, In vitro, law.invention, Concentrative nucleoside transporter, Molecular level, Biochemistry, law, Vibrio cholerae, Recombinant DNA, medicine, biology.protein, Function (biology)
Abstract

Secondary active transporters are responsible for the cellular uptake of many biologically important molecules, including neurotransmitters, nutrients, and drugs. Because of their physiological and clinical importance, a method for assessing their transport activity in vitro is necessary to gain a better understanding of how these transporters function at the molecular level. In this chapter, we describe a protocol for reconstituting the concentrative nucleoside transporter from Vibrio cholerae into proteoliposomes. We then describe a radiolabeled substrate uptake assay that can be used to functionally characterize the transporter. These methods are relatively common and can be applied to other secondary active transporters, with or without some modification.

Published
2015
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5. CNT2, Concentrative Nucleoside Transporter 2

Author

Carol E. Cass, James W. Young, and Stephen A. Baldwin

Subjects
Purine, Concentrative nucleoside transporter, chemistry.chemical_compound, Biochemistry, biology, Chemistry, biology.protein, Substrate (chemistry), Equilibrative nucleoside transporter 2, Nucleoside, Uridine, Transport protein
Abstract

Human CNT2 (hCNT2, hSPNT1 or SLC28A2) is a concentrative Na+-dependent nucleoside transport protein with a substrate preference for purine nucleosides and uridine …

Published
2007
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6. CNT1, Concentrative Nucleoside Transporter 1

Author

James W. Young, Carol E. Cass, and Stephen A. Baldwin

Subjects
Kidney, Pyrimidine, biology, Equilibrative nucleoside transporter, Adenosine, Transport protein, Jejunum, Concentrative nucleoside transporter, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Biochemistry, medicine, biology.protein, Nucleoside, medicine.drug
Abstract

Human CNT1 (hCNT1 or SLC28A1) is a concentrative Na+-dependent nucleoside transport protein found primarily in specialized epithelia (jejunum, liver, kidney) with a substrate preference for pyrimidine nucleosides and adenosine …

Published
2007
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7. Sodium Dependent, Concentrative Nucleoside Transporters

Author

James Young, Carol E. Cass, and Stephen A. Baldwin

Subjects
Concentrative nucleoside transporter, biology, Protein family, Biochemistry, Chemistry, biology.protein, Transporter, Equilibrative nucleoside transporter 2, Sodium dependent, Nucleoside
Abstract

The concentrative nucleoside transporter (CNT or SLC28) protein family in humans is represented by three members, …

Published
2007
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8. Steroid hormones are novel nucleoside transport inhibitors by competition with nucleosides for their transporters.

Author

Kaneko M, Hakuno F, Kamei H, Yamanaka D, Chida K, Minami S, Coe IR, and Takahashi S

Subjects
Animals, Cell Line, Tumor, Dose-Response Relationship, Drug, Gonadal Steroid Hormones administration & dosage, Humans, Myocytes, Cardiac drug effects, Rats, Estradiol administration & dosage, Myocytes, Cardiac metabolism, Neuroblastoma metabolism, Nucleoside Transport Proteins antagonists & inhibitors, Nucleoside Transport Proteins metabolism, Nucleosides metabolism, Progesterone administration & dosage
Abstract

Nucleoside transport is important for nucleic acid synthesis in cells that cannot synthesize nucleosides de novo, and for entry of many cytotoxic nucleoside analog drugs used in chemotherapy. This study demonstrates that various steroid hormones induce inhibition of nucleoside transport in mammalian cells. We analyzed the inhibitory effects of estradiol (E2) on nucleoside transport using SH-SY5Y human neuroblastoma cells. We observed inhibitory effects after acute treatment with E2, which lasted in the presence of E2. However, when E2 was removed, the effect immediately disappeared, suggesting that E2 effects are not mediated through the canonical regulatory pathway of steroid hormones, such as transcriptional regulation. We also discovered that E2 could competitively inhibit thymidine uptake and binding of the labeled nucleoside transporter inhibitor, S-[4-nitrobenzyl]-6-thioinosine (NBTI), indicating that E2 binds to endogenous nucleoside transporters, leading to inhibition of nucleoside transport. We then tested the effects of various steroids on nucleoside uptake in NBTI-sensitive cells, SH-SY5Y and NBTI-insensitive cells H9c2 rat cardiomyoblasts. We found E2 and progesterone clearly inhibited both NBTI-sensitive and insensitive uptake at micromolar concentrations. Taken together, we concluded that steroid hormones function as novel nucleoside transport inhibitors by competition with nucleosides for their transporters., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Published
2014
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