Skip to main content
Log in

Sodium-dependent ascorbic acid transporter family SLC23

  • The ABC of Solute Carriers
  • Guest Editor: Matthias A. Hediger
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

l-Ascorbic acid (vitamin C) is an effective antioxidant and an essential cofactor in numerous enzymatic reactions. Two Na+-dependent vitamin C transporters (SVCT1 and SVCT2) are members of the SLC23 human gene family, which also contains two orphan members. SVCT1 and SVCT2 display similar properties, including high affinity for l-ascorbic acid, but are discretely distributed. SVCT1 is confined to epithelial systems including intestine, kidney, and liver, whereas SVCT2 serves a host of metabolically active and specialized cells and tissues including neurons, the eye, lung, and placenta, and a range of neuroendocrine, exocrine, and endothelial tissues. An SVCT2-knockout mouse reveals an obligatory requirement for SVCT2, but many of the specific roles of this transporter remain unclear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

Notes

  1. The HUGO gene names for SVCT1 and SVCT2 were revised in 2003. SVCT1 is now assigned to SLC23A1 and SVCT2 is now assigned to SLC23A2. See http://www.gene.ucl.ac.uk/nomenclature/

References

  1. Berger UV, Hediger MA (2000) The vitamin C transporter SVCT2 is expressed by astrocytes in culture but not in situ. Neuroreport 11:1395–1399

    CAS  PubMed  Google Scholar 

  2. Berger UV, Li X-CM, Liu W, Tang Z, Slusher BS, Hediger MA (2003) Ischemia-induced upregulation of mRNA for the sodium-coupled vitamin C transporter SVCT2 in neurons and astrocytes. J Neurochem Vol 86 Issue 4 (August 2003)

  3. Brown LAS, Jones DP (1996) The biology of ascorbic acid. In: Cadenas E, Packer L (eds) Handbook of antioxidants. Dekker, New York, pp 117–154

  4. Castro M, Caprile T, Astuya A, Millan C, Reinicke K, Vera JC, Vasquez O, Aguayo LG, Nualart F (2001) High-affinity sodium-vitamin C co-transporters (SVCT) expression in embryonic mouse neurons. J Neurochem 78:815–823

    Article  CAS  PubMed  Google Scholar 

  5. Clark AG, Rohrbaugh AL, Otterness I, Kraus VB (2002) The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants. Matrix Biol 21:175–184

    Article  CAS  PubMed  Google Scholar 

  6. Daruwala R, Song J, Koh WS, Rumsey SC, Levine M (1999) Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett 460:480–484

    Article  CAS  PubMed  Google Scholar 

  7. Dhariwal KR, Hartzell WO, Levine M (1991) Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. Am J Clin Nutr 54:712–716

    CAS  PubMed  Google Scholar 

  8. Englard S, Seifter S (1986) The biochemical functions of ascorbic acid. Annu Rev Nutr 6:365–406

    Article  CAS  PubMed  Google Scholar 

  9. Erichsen HC, Eck P, Levine M, Chanock S (2001) Characterization of the genomic structure of the human vitamin C transporter SVCT1 (SLC23A2). J Nutr 131:2623–2627

    CAS  PubMed  Google Scholar 

  10. Faaland CA, Race JE, Ricken G, Warner FJ, Williams WJ, Holtzman EJ (1998) Molecular characterization of two novel transporters from human and mouse kidney and from LLC-PK1 cells reveals a novel conserved family that is homologous to bacterial and Aspergillus nucleobase transporters. Biochim Biophys Acta 1442:353–360

    Article  CAS  PubMed  Google Scholar 

  11. Guimarães MJ, Bazan JF, Zlotnik A, Wiles MV, Grimaldi JC, Lee F, McClanahan T (1995) A new approach to the study of haematopoietic development in the yolk sac and embryoid tissues. Development 121:3335–3346

    PubMed  Google Scholar 

  12. Hammarström L (1966) Autoradiographic studies on the distribution of C14-labelled ascorbic acid and dehydroascorbic acid. Acta Physiol Scand 70 [Suppl] 289:1–75

    Google Scholar 

  13. Helbig H, Korbmacher C, Wohlfarth J, Berweck S, Kühner D, Wiederholt M (1989) Electrogenic Na+-ascorbate cotransport in cultured bovine pigmented ciliary epithelial cells. Am J Physiol 256:C44–C49

    CAS  PubMed  Google Scholar 

  14. Hogue DL, Ling V (1999) A human nucleobase transporter-like cDNA (SLC23A1): member of a transporter family conserved from bacteria to mammals. Genomics 59:18–23

    Article  CAS  PubMed  Google Scholar 

  15. Jacob RA, Sotoudeh G (2002) Vitamin C function and status in chronic disease. Nutr Clin Care 5:66–74

    Article  PubMed  Google Scholar 

  16. Kannan R, Stolz A, Ji Q, Prasad PD, Ganapathy V (2001) Vitamin C transport in human lens epithelial cells: evidence for the presence of SVCT2. Exp Eye Res 73:159–165

    Article  CAS  PubMed  Google Scholar 

  17. Korcok J, Yan R, Siushansian R, Dixon SJ, Wilson JX (2000) Sodium-ascorbate cotransport controls intracellular ascorbate concentration in primary astrocyte cultures expressing the SVCT2 transporter. Brain Res 881:144–151

    Article  CAS  PubMed  Google Scholar 

  18. Liang W-J, Johnson D, Ma L-S, Jarvis SM (2002) Regulation of the human vitamin C transporters expressed in COS-1 cells by protein kinase C. Am J Physiol 283:C1696–C1704

    CAS  Google Scholar 

  19. MacDonald L, Thumser AE, Sharp P (2002) Decreased expression of the vitamin C transporter SVCT1 by ascorbic acid in a human intestinal epithelial cell line. Br J Nutr 87:97–100

    Article  CAS  PubMed  Google Scholar 

  20. Maulén NP, Henríquez EA, Kempe S, Cárcamo JG, Smid-Kotsas A, Bachem M, Grunen A, Bustamante ME, Nualart F, Vera JC (2003) Upregulation and polarized expression of the sodium-ascorbic acid transporter SVCT1 in post-confluent differentiated CaCo-2 cells. J Biol Chem 278:9035–9041

    Article  PubMed  Google Scholar 

  21. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (1996) Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res 3:321–354

    CAS  PubMed  Google Scholar 

  22. Padh H (1991) Vitamin C: newer insights into its biochemical functions. Nutr Rev 49:65–70

    CAS  PubMed  Google Scholar 

  23. Page RDM (1996) TreeView: an application to display phylogenetic trees on personal computers. Comput Appl Biosci 12:357–358

    CAS  PubMed  Google Scholar 

  24. Rajan DP, Huang W, Dutta B, Devoe LD, Leibach FH, Ganapathy V, Prasad PD (1999) Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function. Biochem Biophys Res Commun 262:762–768

    Article  CAS  PubMed  Google Scholar 

  25. Reiss GR, Werness PG, Zollman PE, Brubaker RF (1986) Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals. Arch Ophthalmol 104:753–755

    CAS  PubMed  Google Scholar 

  26. Rice ME (2000) Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci 23:209–216

    Article  CAS  PubMed  Google Scholar 

  27. Rice ME, Lee EJ, Choy Y (1995) High levels of ascorbic acid, not glutathione, in the CNS of anoxia-tolerant reptiles contrasted with levels in anoxia-intolerant species. J Neurochem 64:1790–1799

    CAS  PubMed  Google Scholar 

  28. Rose RC, Bode AM (1991) Ocular ascorbate transport and metabolism. Comp Biochem Physiol 100:273–285

    Article  CAS  Google Scholar 

  29. Rose RC, Bode AM (1993) Biology of free radical scavengers: an evaluation of ascorbate. FASEB J 7:1135–1142

    CAS  PubMed  Google Scholar 

  30. Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M (1997) Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J Biol Chem 272:18982–18989

    Article  CAS  PubMed  Google Scholar 

  31. Rumsey SC, Welch RW, Garraffo HM, Ge P, Lu SF, Crossman AT, Kirk KL, Levine M (1999) Specificity of ascorbate analogs for ascorbate transport. Synthesis and detection of [125I]6-deoxy-6-iodo-l-ascorbic acid and characterization of its ascorbate-specific transport properties. J Biol Chem 274:23215–23222

    Article  CAS  PubMed  Google Scholar 

  32. Rumsey SC, Daruwala R, Al-Hasani H, Zarnowski MJ, Simpson IA, Levine M (2000) Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J Biol Chem 275:28246–28253

    CAS  PubMed  Google Scholar 

  33. Song J, Kwon O, Chen S, Daruwala R, Eck P, Park JB, Levine M (2002) Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose. J Biol Chem 277:15252–15260

    Article  CAS  PubMed  Google Scholar 

  34. Sotiriou S, Gispert S, Cheng J, Wang Y, Chen A, Hoogstraten-Miller S, Miller GF, Kwon O, Levine M, Guttentag SH, Nussbaum RL (2002) Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med 8:514–517

    Article  CAS  PubMed  Google Scholar 

  35. Stratakis CA, Taymans SE, Daruwala R, Song J, Levine M (2000) Mapping of the human genes (SLC23A2 and SLC23A1) coding for vitamin C transporters 1 and 2 (SVCT1 and SVCT2) to 5q23 and 20p12, respectively. J Med Genet 37:E20

    Article  CAS  PubMed  Google Scholar 

  36. Takanaga, Hitomi, Mackenzie, Bryan, Hediger, Matthias A. (2003) Tissue distribution, functional characterization and gene structures of vitamin C transporter isoforms (abstract). FASEB J 17:A908

    Google Scholar 

  37. Tatusova TA, Madden TL (1999) BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiol Lett 174:247–250

    CAS  PubMed  Google Scholar 

  38. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    PubMed  Google Scholar 

  39. Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen X-Z, Wang Y, Brubaker RF, Hediger MA (1999) A family of mammalian Na+-dependent l-ascorbic acid transporters. Nature 399:70–75

    Article  CAS  PubMed  Google Scholar 

  40. Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen X-Z, Wang Y, Brubaker RF, Hediger MA (1999) A family of mammalian Na+-dependent l-ascorbic acid transporters. Nature 399:70–75. Supplementary information at www.nature.com

    Article  CAS  PubMed  Google Scholar 

  41. Vera JC, Rivas CI, Fischbarg J (1993) Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature 364:79–82

    CAS  PubMed  Google Scholar 

  42. Wang H, Dutta B, Huang W, Devoe LD, Leibach FH, Ganapathy V, Prasad PD (1999) Human Na+-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant. Biochim Biophys Acta 1461:1–9

    Article  CAS  PubMed  Google Scholar 

  43. Wang Y, Mackenzie B, Tsukaguchi H, Weremowicz S, Morton CC, Hediger MA (2000) Human vitamin C (l-ascorbic acid) transporter SVCT1. Biochem Biophys Res Commun 267:488–494

    Article  CAS  PubMed  Google Scholar 

  44. Wilson JX (1997) Antioxidant defense of the brain: a role for astrocytes. Can J Physiol Pharmacol 75:1149–1163

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthias A. Hediger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takanaga, H., Mackenzie, B. & Hediger, M.A. Sodium-dependent ascorbic acid transporter family SLC23. Pflugers Arch - Eur J Physiol 447, 677–682 (2004). https://doi.org/10.1007/s00424-003-1104-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-003-1104-1

Keywords

Navigation