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Cited by 661Vitamin C and Antioxidants ResearchAntioxidant Activity and Oxidative StressAmino Acid Enzymes and Metabolism

Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2

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Harrison, Fiona E., May, James M.·2009·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2008.12.018PMC PMC2649700
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Abstract

Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it also has a number of other important functions, participating as a cofactor in several enzyme reactions, including catecholamine synthesis, collagen production, and regulation of HIF-1 alpha. Ascorbate is transported into the brain and neurons via the sodium-dependent vitamin C transporter 2 (SVCT2), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters of the GLUT family. Once in cells, it is rapidly reduced to ascorbate. The highest concentrations of ascorbate in the body are found in the brain and in neuroendocrine tissues such as adrenal, although the brain is the most difficult organ to deplete of ascorbate. Combined with regional asymmetry in ascorbate distribution within different brain areas, these facts suggest an important role for ascorbate in the brain. Ascorbate is proposed as a neuromodulator of glutamatergic, dopaminergic, cholinergic, and GABAergic transmission and related behaviors. Neurodegenerative diseases typically involve high levels of oxidative stress and thus ascorbate has been posited to have potential therapeutic roles against ischemic stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease.

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  1. [21]Tsukaguchi H Tokui T Mackenzie B Berger UV Chen XZ Wang YX Brubaker RF Hediger MA A family of mammalian Na+-dependent L-ascorbic acid transporters Nature 399 70 75 1999 10331392
  2. [23]Tsukaguchi H Tokui T Mackenzie B Berger UV Chen XZ Wang YX Brubaker RF Hediger MA A family of mammalian Na+-dependent L-ascorbic acid transporters Nature 399 70 75 1999 10331392
  3. [24]Tsukaguchi H Tokui T Mackenzie B Berger UV Chen XZ Wang YX Brubaker RF Hediger MA A family of mammalian Na+-dependent L-ascorbic acid transporters Nature 399 70 75 1999 10331392
  4. [25]Tsukaguchi H Tokui T Mackenzie B Berger UV Chen XZ Wang YX Brubaker RF Hediger MA A family of mammalian Na+-dependent L-ascorbic acid transporters Nature 399 70 75 1999 10331392
  5. [47]Angelow S Haselbach M Galla HJ Functional characterisation of the active ascorbic acid transport into cerebrospinal fluid using primary cultured choroid plexus cells Brain Res 988 105 113 2003 14519531
  6. [48]Angelow S Haselbach M Galla HJ Functional characterisation of the active ascorbic acid transport into cerebrospinal fluid using primary cultured choroid plexus cells Brain Res 988 105 113 2003 14519531
  7. [49]Hakvoort A Haselbach M Galla HJ Active transport properties of porcine choroid plexus cells in culture Brain Res 795 247 256 1998 9622643
  8. [50]Angelow S Haselbach M Galla HJ Functional characterisation of the active ascorbic acid transport into cerebrospinal fluid using primary cultured choroid plexus cells Brain Res 988 105 113 2003 14519531
  9. [51]Hakvoort A Haselbach M Galla HJ Active transport properties of porcine choroid plexus cells in culture Brain Res 795 247 256 1998 9622643
  10. [57]García ML Salazar K Millán C Rodríguez F Montecinos H Caprile T Silva C Cortes C Reinicke K Vera JC Aguayo LG Olate J Molina B Nualart F Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells Glia 50 32 47 2005 15625716
  11. [58]García ML Salazar K Millán C Rodríguez F Montecinos H Caprile T Silva C Cortes C Reinicke K Vera JC Aguayo LG Olate J Molina B Nualart F Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells Glia 50 32 47 2005 15625716
  12. [60]García ML Salazar K Millán C Rodríguez F Montecinos H Caprile T Silva C Cortes C Reinicke K Vera JC Aguayo LG Olate J Molina B Nualart F Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells Glia 50 32 47 2005 15625716
  13. [62]García ML Salazar K Millán C Rodríguez F Montecinos H Caprile T Silva C Cortes C Reinicke K Vera JC Aguayo LG Olate J Molina B Nualart F Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells Glia 50 32 47 2005 15625716
  14. [63]García ML Salazar K Millán C Rodríguez F Montecinos H Caprile T Silva C Cortes C Reinicke K Vera JC Aguayo LG Olate J Molina B Nualart F Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells Glia 50 32 47 2005 15625716
  15. [66]Montel-Hagen A Kinet S Manel N Mongellaz C Prohaska R Battini JL Delaunay J Sitbon M Taylor N Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C Cell 132 1039 1048 2008 18358815
  16. [67]Montel-Hagen A Kinet S Manel N Mongellaz C Prohaska R Battini JL Delaunay J Sitbon M Taylor N Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C Cell 132 1039 1048 2008 18358815
  17. [70]Tsukaguchi H Tokui T Mackenzie B Berger UV Chen XZ Wang YX Brubaker RF Hediger MA A family of mammalian Na+-dependent L-ascorbic acid transporters Nature 399 70 75 1999 10331392
  18. [78]Castro M Caprile T Astuya A Millán C Reinicke K Vera JC Vásquez O Aguayo LG Nualart F High-affinity sodium-vitamin C co-transporters (SVCT) expression in embryonic mouse neurons J Neurochem 78 815 823 2001 11520902
  19. [87]Rice ME Russo-Menna I Differential compartmentalization of brain ascorbate and glutathione between neurons and glia Neuroscience 82 1213 1223 1998 9466441
  20. [88]Castro M Caprile T Astuya A Millán C Reinicke K Vera JC Vásquez O Aguayo LG Nualart F High-affinity sodium-vitamin C co-transporters (SVCT) expression in embryonic mouse neurons J Neurochem 78 815 823 2001 11520902
  21. [89]Rice ME Russo-Menna I Differential compartmentalization of brain ascorbate and glutathione between neurons and glia Neuroscience 82 1213 1223 1998 9466441
  22. [90]Nualart FJ Rivas CI Montecinos VP Godoy AS Guaiquil VH Golde DW Vera JC Recycling of vitamin C by a bystander effect J Biol Chem 278 10128 10133 2003 12435736
  23. [91]Berger UV Lu XC Liu W Tang Z Slusher BS Hediger MA Effect of middle cerebral artery occlusion on mRNA expression for the sodium-coupled vitamin C transporter SVCT2 in rat brain J Neurochem 86 896 906 2003 12887688
  24. [94]Astuya A Caprile T Castro M Salazar K García MD Reinicke K Rodríguez F Vera JC Millán C Ulloa V Low M Martínez F Nualart F Vitamin C uptake and recycling among normal and tumor cells from the central nervous system J Neurosci Res 79 146 156 2005 15578707
  25. [95]Berger UV Lu XC Liu W Tang Z Slusher BS Hediger MA Effect of middle cerebral artery occlusion on mRNA expression for the sodium-coupled vitamin C transporter SVCT2 in rat brain J Neurochem 86 896 906 2003 12887688
  26. [96]Rice ME Ascorbate regulation and its neuroprotective role in the brain Trends Neurosci 23 209 216 2000 10782126
  27. [97]Rice ME Ascorbate regulation and its neuroprotective role in the brain Trends Neurosci 23 209 216 2000 10782126
  28. [103]Cammack J Ghasemzadeh B Adams RN The pharmacological profile of glutamate-evoked ascorbic acid efflux measured by in vivo electrochemistry Brain Res 565 17 22 1991 1685348
  29. [109]May JM Li L Hayslett K Qu ZC Ascorbate transport and recycling by SH-SY5Y neuroblastoma cells: Response to glutamate toxicity Neurochem Res 31 785 794 2006 16791474
  30. [110]Jackson TS Xu AM Vita JA Keaney JF Jr Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations Circ Res 83 916 922 1998 9797340
  31. [117]Kratzing CC Kelly JD Kratzing JE Ascorbic acid in fetal rat brain J Neurochem 44 1623 1624 1985 3989554
  32. [122]Qiu S Li L Weeber EJ May JM Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity J Neurosci Res 85 1046 1056 2007 17304569
  33. [127]Wakefield LM Cass AE Radda GK Electron transfer across the chromaffin granule membrane. Use of EPR to demonstrate reduction of intravesicular ascorbate radical by the extravesicular mitochondrial NADH:ascorbate radical oxidoreductase J Biol Chem 261 9746 9752 1986 3015905
  34. [131]Rebec GV Witowski SR Sandstrom MI Rostand RD Kennedy RT Extracellular ascorbate modulates cortically evoked glutamate dynamics in rat striatum Neurosci Lett 378 166 170 2005 15781152
  35. [137]Rice ME Ascorbate regulation and its neuroprotective role in the brain Trends Neurosci 23 209 216 2000 10782126
  36. [139]Mefford IN Oke AF Adams RN Regional distribution of ascorbate in human brain Brain Res 212 223 226 1981 7225858
  37. [147]Desole MS Miele M Enrico P Esposito G Fresu L De Natale G Miele E Investigations into the relationship between the dopaminergic system and ascorbic acid in rat striatum Neurosci Lett 127 34 38 1991 1881615
  38. [148]Saponjic RM Mueller K Krug D Kunko PM The effects of haloperidol, scopolamine, and MK-801 on amphetamine-induced increases in ascorbic and uric acid as determined by voltammetry in vivo Pharmacol Biochem Behav 48 161 168 1994 8029286
  39. [154]Parle M Dhingra D Ascorbic Acid: a promising memory-enhancer in mice J Pharmacol Sci 93 129 135 2003 14578579
  40. [155]De Angelis L Furlan C The effects of ascorbic acid and oxiracetam on scopolamine-induced amnesia in a habituation test in aged mice Neurobiol Learn Mem 64 119 124 1995 7582819
  41. [160]Harrison FE Yu SS Van Den Bossche KL Li L May JM McDonald MP Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid J Neurochem 106 1198 1208 2008 18466336 PMC2575028
  42. [161]Desole MS Anania V Esposito G Carboni F Senini A Miele E Neurochemical and behavioural changes induced by ascorbic acid and d-amphetamine in the rat Pharmacol Res Commun 19 441 450 1987 3659117
  43. [167]Desole MS Miele M Esposito G Enrico P Fresu L De Natale G Miele E Further investigations into the relationship between the dopaminergic system, ascorbic acid and uric acid in the rat striatum Eur J Pharmacol 205 97 100 1991 1812002
  44. [170]Sotiriou S Gispert S Cheng J Wang YH Chen A Hoogstraten-Miller S Miller GF Kwon O Levine M Guttentag SH Nussbaum RL Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival Nature Med 8 514 517 2002 11984597
  45. [177]Hughes RE Hurley RJ Jones PR The retention of ascorbic acid by guinea-pig tissues Br J Nutr 26 433 438 1971 5157948
  46. [178]Hill KE Montine TJ Motley AK Li X May JM Burk RF Combined deficiency of vitamins E and C causes paralysis and death in guinea pigs Am J Clin Nutr 77 1484 1488 2003 12791628
  47. [180]Sotiriou S Gispert S Cheng J Wang YH Chen A Hoogstraten-Miller S Miller GF Kwon O Levine M Guttentag SH Nussbaum RL Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival Nature Med 8 514 517 2002 11984597
  48. [182]Sotiriou S Gispert S Cheng J Wang YH Chen A Hoogstraten-Miller S Miller GF Kwon O Levine M Guttentag SH Nussbaum RL Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival Nature Med 8 514 517 2002 11984597
  49. [183]Sotiriou S Gispert S Cheng J Wang YH Chen A Hoogstraten-Miller S Miller GF Kwon O Levine M Guttentag SH Nussbaum RL Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival Nature Med 8 514 517 2002 11984597
  50. [194]Qiu S Li L Weeber EJ May JM Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity J Neurosci Res 85 1046 1056 2007 17304569
  51. [195]Berger UV Lu XC Liu W Tang Z Slusher BS Hediger MA Effect of middle cerebral artery occlusion on mRNA expression for the sodium-coupled vitamin C transporter SVCT2 in rat brain J Neurochem 86 896 906 2003 12887688
  52. [199]Montine T Neely M Quinn J Beal M Markesbery W Roberts L Morrow J Lipid peroxidation in aging brain and Alzheimer's disease Free Radic Biol Med 33 620 626 2002 12208348

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Authors
Harrison, F. E., & May, J. M.
Affiliations
Vanderbilt University (US)
Corresponding author
May, James M.
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2009-03
Volume
46
Issue
6
Pages
719-730
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2008.12.018
PMC
PMC2649700
OpenAlex
W1973602321
Cited by
661
References
169
Citations by year
2026: 28 · 2025: 43 · 2024: 45 · 2023: 35 · 2022: 47 · 2021: 45 · 2020: 46 · 2019: 40 · 2018: 52 · 2017: 40 · 2016: 26 · 2015: 34 · 2014: 40 · 2013: 41 · 2012: 39
FWCI
3.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK050435, DK-50435)
  • National Institute of Neurological Disorders and Stroke (R01NS057674)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
vitamin C, SVCT2, brain, dehydroascorbic acid, GLUT transporters, antioxidants, catecholamine synthesis, HIF-1α, oxidative stress, neurodegenerative diseases, ischemic stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, neuromodulation
MeSH terms
Animals, Antioxidants, Ascorbic Acid, Biological Transport, Brain, Humans, Ischemia, Synaptic Transmission, Neurons, Oxidative Stress, Neurodegenerative Diseases, Symporters, Organic Anion Transporters, Sodium-Dependent, Sodium-Coupled Vitamin C Transporters

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