SVCT2/SLC23A2 is a sodium-dependent urate transporter : functional properties and practical application
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Urate transporters play a pivotal role in urate handling in the human body, but the urate transporters identified to date do not account for all known molecular processes of urate handling, suggesting the presence of latent machineries. We recently showed that a urate transporter SLC2A12 is also a physiologically important exporter of ascorbate (the main form of vitamin C in the body) that would cooperate with an ascorbate importer, sodium-dependent vitamin C transporter 2 (SVCT2). Based on the dual functions of SLC2A12 and cooperativity between SLC2A12 and SVCT2, we hypothesized that SVCT2 might be able to transport urate. To test this proposal, we conducted cell-based analyses using SVCT2-expressing mammalian cells. The results demonstrated that SVCT2 is a novel urate transporter. Vitamin C inhibited SVCT2-mediated urate transport with a half-maximal inhibitory concentration of 36.59 μM, suggesting that the urate transport activity may be sensitive to physiological ascorbate levels in blood. Similar results were obtained for mouse Svct2. Further, using SVCT2 as a sodium-dependent urate importer, we established a cell-based urate efflux assay that will be useful for identification of other novel urate exporters as well as functional characterization of nonsynonymous variants of already-identified urate exporters including ATP-binding cassette transporter G2. While more studies will be needed to elucidate the physiological impact of SVCT2-mediated urate transport, our findings deepen understanding of urate transport machineries.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:299 |
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| Enthalten in: |
The Journal of biological chemistry - 299(2023), 8 vom: 24. Aug., Seite 104976 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Toyoda, Yu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.08.2023 Date Revised 06.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jbc.2023.104976 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358922348 |
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| 100 | 1 | |a Toyoda, Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SVCT2/SLC23A2 is a sodium-dependent urate transporter |b functional properties and practical application |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 31.08.2023 | ||
| 500 | |a Date Revised 06.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Urate transporters play a pivotal role in urate handling in the human body, but the urate transporters identified to date do not account for all known molecular processes of urate handling, suggesting the presence of latent machineries. We recently showed that a urate transporter SLC2A12 is also a physiologically important exporter of ascorbate (the main form of vitamin C in the body) that would cooperate with an ascorbate importer, sodium-dependent vitamin C transporter 2 (SVCT2). Based on the dual functions of SLC2A12 and cooperativity between SLC2A12 and SVCT2, we hypothesized that SVCT2 might be able to transport urate. To test this proposal, we conducted cell-based analyses using SVCT2-expressing mammalian cells. The results demonstrated that SVCT2 is a novel urate transporter. Vitamin C inhibited SVCT2-mediated urate transport with a half-maximal inhibitory concentration of 36.59 μM, suggesting that the urate transport activity may be sensitive to physiological ascorbate levels in blood. Similar results were obtained for mouse Svct2. Further, using SVCT2 as a sodium-dependent urate importer, we established a cell-based urate efflux assay that will be useful for identification of other novel urate exporters as well as functional characterization of nonsynonymous variants of already-identified urate exporters including ATP-binding cassette transporter G2. While more studies will be needed to elucidate the physiological impact of SVCT2-mediated urate transport, our findings deepen understanding of urate transport machineries | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ABCG2 | |
| 650 | 4 | |a anion transport | |
| 650 | 4 | |a ascorbate | |
| 650 | 4 | |a ascorbic acid | |
| 650 | 4 | |a cell-based urate efflux assay | |
| 650 | 4 | |a purine | |
| 650 | 4 | |a urate importer | |
| 650 | 4 | |a uric acid | |
| 650 | 4 | |a vitamin C transporter | |
| 650 | 7 | |a Ascorbic Acid |2 NLM | |
| 650 | 7 | |a PQ6CK8PD0R |2 NLM | |
| 650 | 7 | |a Organic Anion Transporters, Sodium-Dependent |2 NLM | |
| 650 | 7 | |a Sodium-Coupled Vitamin C Transporters |2 NLM | |
| 650 | 7 | |a urate transporter |2 NLM | |
| 650 | 7 | |a Uric Acid |2 NLM | |
| 650 | 7 | |a 268B43MJ25 |2 NLM | |
| 650 | 7 | |a SLC23A2 protein, human |2 NLM | |
| 650 | 7 | |a Slc23a2 protein, mouse |2 NLM | |
| 700 | 1 | |a Miyata, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Shigesawa, Ryuichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuo, Hirotaka |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Takada, Tappei |e verfasserin |4 aut | |
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