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Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice
Open accessAbstract
Levels of the necessary nutrient vitamin C (ascorbate) are tightly regulated by intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Ascorbate levels are controlled in part by regulation of transport through at least 2 sodium-dependent transporters: Slc23a1 and Slc23a2 (also known as Svct1 and Svct2, respectively). Previous work indicates that Slc23a2 is essential for viability in mice, but the roles of Slc23a1 for viability and in adult physiology have not been determined. To investigate the contributions of Slc23a1 to plasma and tissue ascorbate concentrations in vivo, we generated Slc23a1-/- mice. Compared with wild-type mice, Slc23a1-/- mice increased ascorbate fractional excretion up to 18-fold. Hepatic portal ascorbate accumulation was nearly abolished, whereas intestinal absorption was marginally affected. Both heterozygous and knockout pups born to Slc23a1-/- dams exhibited approximately 45% perinatal mortality, and this was associated with lower plasma ascorbate concentrations in dams and pups. Perinatal mortality of Slc23a1-/- pups born to Slc23a1-/- dams was prevented by ascorbate supplementation during pregnancy. Taken together, these data indicate that ascorbate provided by the dam influenced perinatal survival. Although Slc23a1-/- mice lost as much as 70% of their ascorbate body stores in urine daily, we observed an unanticipated compensatory increase in ascorbate synthesis. These findings indicate a key role for Slc23a1 in renal ascorbate absorption and perinatal survival and reveal regulation of vitamin C biosynthesis in mice.
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“These SNPs are more common in the African and African-American populations over others, while SNPs of Slc23A2 are of a similar frequency in the Caucasian and African populations [80,82,84].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [80]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“SNPs of SLC23A1 were characterized as both synonymous and non-synonymous SNPs (with the greatest diversity found in the African population) producing proteins of lower functionality.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [80]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Vitamin C is efficiently and saturably reabsorbed from the urinary tract, and SVCT1 plays an important role, as documented by knockout Slc23a1−/− mice with an 18-fold higher ascorbate excretion [51,80,81].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [80]
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“The strongest evidence to decrease circulating vitamin C levels was found for several common SNPs of SLC23A1 due to reduced renal reabsorption.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [80]
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“However, an elevation of vitamin C levels was also seldomly described [80,82,83].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [80]
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“In the case of SNPs of SLC23A2, all studied polymorphisms were synonymous [80,83].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [80]
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Cites
A simple salting out procedure for extracting DNA from human nucleated cells
Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.3.1215 · Cited by 20,341
The National Center for Biotechnology Information
Benson, D. A., Boguski, M. S., Lipman, D. J., & Ostell, J. (1990) · Genomics · doi:10.1016/0888-7543(90)90583-g · Cited by 5,109
Manipulating the mouse embryo: A laboratory manual
Hogan, B. L. M., Costantini, F. D., & Lacy, E. (1986) · Cited by 4,460
Recommended Dietary Allowances.
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-9-822_3 · Cited by 3,926
Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance
Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3704 · Cited by 1,325
Vitamin C pharmacokinetics: Implications for oral and intravenous use
Padayatty, S. J., Sun, H., Wang, Y., Riordan, H. D., Hewitt, S. M., Katz, A., Wesley, R. A., & Levine, M. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-7-200404060-00010 · Cited by 992
A family of mammalian Na+-dependent L-ascorbic acid transporters
Tsukaguchi, H., Tokui, T., Mackenzie, B., Berger, U. V., Chen, X.-Z., Wang, Y., Brubaker, R. F., & Hediger, M. A. (1999) · Nature · doi:10.1038/19986 · Cited by 882
Chappell, L. C., Seed, P. T., Briley, A. L., Kelly, F. J., Lee, R., Hunt, B. J., Parmar, K., Bewley, S., Shennan, A. H., Steer, P. J., et al. (1999) · The Lancet · doi:10.1016/s0140-6736(99)80010-5 · Cited by 784
New Concepts in the Biology and Biochemistry of Ascorbic Acid
Flier, J. S., Underhill, L. H., & Levine, M. (1986) · New England Journal of Medicine · doi:10.1056/nejm198604033141407 · Cited by 646
Criteria and recommendations for vitamin C intake
Levine, M. (1999) · JAMA · doi:10.1001/jama.281.15.1415 · Cited by 559
Self-citationWhittaker, P., Kloner, R. A., Boughner, D. R., & Pickering, J. G. (1994) · Basic Research in Cardiology · doi:10.1007/bf00788278 · Cited by 496
A new recommended dietary allowance of vitamin C for healthy young women
Levine, M., Wang, Y., Padayatty, S. J., & Morrow, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171318198 · Cited by 496
Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid
Vera, J. C., Rivas, C. I., Fischbarg, J., & Golde, D. W. (1993) · Nature · doi:10.1038/364079a0 · Cited by 492
Glucose Transporter Isoforms GLUT1 and GLUT3 Transport Dehydroascorbic Acid
Rumsey, S. C., Kwon, O., Xu, G. W., Burant, C., Simpson, I. A., & Levine, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.30.18982 · Cited by 481
Vitamins C and E and the Risks of Preeclampsia and Perinatal Complications
Rumbold, A. R., Crowther, C. A., Haslam, R. R., Dekker, G., & Robinson, J. S. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054186 · Cited by 466
SAGEmap: A Public Gene Expression ResourcePreprint
Lash, A., Tolstoshev, C. M., Wagner, L., Schuler, G. D., Strausberg, R. L., Riggins, G. J., & Altschul, S. F. (2000) · Genome Research · doi:10.1101/gr.10.7.1051 · Cited by 418
Ames, B. N. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608757103 · Cited by 411
Sotiriou, S., Gispert, S., Cheng, J., Wang, Y., Chen, A., Hoogstraten-Miller, S., Miller, G. F., Kwon, O., Levine, M., Guttentag, S. H., et al. (2002) · Nature Medicine · doi:10.1038/0502-514 · Cited by 367
Serial determination of glomerular filtration rate in conscious mice using FITC-inulin clearance
Qi, Z., Whitt, I. Z., Mehta, A., Jin, J., Zhao, M., Harris, R. C., Fogo, A. B., & Breyer, M. D. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00324.2003 · Cited by 325
Ames, B. N., Elson‐Schwab, I., & Silver, E. A. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.4.616 · Cited by 319
Ascorbic acid recycling in human neutrophils
Washko, P., Wang, Y., & Levine, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82289-x · Cited by 289
Measurement of Kidney Function
Stevens, L. A., & Levey, A. S. (2005) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.11.009 · Cited by 275
Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum
Dhariwal, K., Hartzell, W., & Levine, M. (1991) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/54.4.712 · Cited by 262
Aortic wall damage in mice unable to synthesize ascorbic acid
Maeda, N., Hagihara, H., Nakata, Y., Hiller, S., Wilder, J., & Reddick, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.841 · Cited by 260
Kondo, Y., Inai, Y., Sato, Y., Handa, S., Kubo, S., Shimokado, K., Goto, S., Nishikimi, M., Maruyama, N., & Ishigami, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511225103 · Cited by 230
Utility of endogenous creatinine clearance as a measure of renal function in mice
Dunn, S., Qi, Z., Böttinger, E. P., Breyer, M. D., & Sharma, K. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00600.x · Cited by 199
Major contribution of tubular secretion to creatinine clearance in mice
Eisner, C. B., Faulhaber‐Walter, R., Wang, Y., Leelahavanichkul, A., Yuen, P. S. T., Mizel, D. E., Star, R. A., Briggs, J. P., Levine, M., & Schnermann, J. B. (2009) · Kidney International · doi:10.1038/ki.2009.501 · Cited by 189
A panoramic view of gene expression in the human kidney
Chabardès, D., Méjean, A., Aude, J.-C., Cheval, L., Stefano, A. D., Gaillard, M., Imbert–Teboul, M., Wittner, M., Balian, C., Anthouard, V., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234604100 · Cited by 176
Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion
Graumlich, J. F., Ludden, T. M., Conry-Cantilena, C., Cantilena, L. R., Wang, Y., & Levine, M. (1997) · Pharmaceutical Research · doi:10.1023/a:1012186203165 · Cited by 172
Self-citationBeazley, D., Ahokas, R. A., Livingston, J., Griggs, M., & Sibai, B. M. (2005) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.09.005 · Cited by 159
A simplified method for HPLC determination of creatinine in mouse serum
Yuen, P. S. T., Dunn, S., Miyaji, T., Yasuda, H., Sharma, K., & Star, R. A. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00366.2003 · Cited by 139
Biochemistry and Molecular Biology of Ascorbic Acid Biosynthesis
Nishikimi, M., & Yagi, K. (1996) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-1-4613-0325-1_2 · Cited by 120
Burns, J. J., Evans, C. D., & Trousof, N. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)70758-8 · Cited by 102
Vitamin C intake and the risk of preterm delivery
Siega‐Riz, A. M., Promislow, J. H. E., Savitz, D. A., Thorp, J. M., & McDonald, T. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1067/s0002-9378(03)00363-6 · Cited by 100
Chen, L., Kim, S. M., Oppermann, M., Faulhaber‐Walter, R., Huang, Y. G., Mizel, D. E., Chen, M., Sequeira-Lόpez, M. L. S., Weinstein, L. S., Gómez, R. A., et al. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00193.2006 · Cited by 97
6-Bromo-6-deoxy-l-ascorbic Acid
Corpe, C. P., Lee, J.-H., Kwon, O., Eck, P., Narayanan, J., Kirk, K. L., & Levine, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412925200 · Cited by 95
Self-citationLack of A1 Adenosine Receptors Augments Diabetic Hyperfiltration and Glomerular Injury
Faulhaber‐Walter, R., Chen, L., Oppermann, M., Kim, S. M., Huang, Y. G., Hiramatsu, N., Mizel, D. E., Kajiyama, H., Zerfas, P. M., Briggs, J. P., et al. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007060721 · Cited by 90
Erichsen, H. C., Engel, S. A. M., Eck, P. K., Welch, R., Yeager, M., Levine, M., Siega-Riz, A. M., Olshan, A. F., & Chanock, S. J. (2006) · American Journal of Epidemiology · doi:10.1093/aje/kwj035 · Cited by 79
Self-citationEck, P., Erichsen, H. C., Taylor, J. G., Yeager, M., Hughes, A., Levine, M., & Chanock, S. (2004) · Human Genetics · doi:10.1007/s00439-004-1167-x · Cited by 69
Ascorbic acid and in situ kinetics: a new approach to vitamin requirements
Levine, M., Dhariwal, K., Washko, P. W., Butler, J., Welch, R., Wang, Y. H., & Bergsten, P. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/54.6.1157s · Cited by 47
Furusawa, H., Sato, Y., Tanaka, Y., Inai, Y., Amano, A., Iwama, M., Kondo, Y., Handa, S., Murata, A., Nishikimi, M., et al. (2008) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.31.1673 · Cited by 42
Sotiriou, S., Gispert, S., Cheng, J., et al. (2002) · Nature Medicine · doi:10.1038/nm0502-514 · Cited by 40
(2004) · Taylor & Francis eBooks · doi:10.1201/9780203500002 · Cited by 28
Meisel, J. L., & Mark, E. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199512213332508 · Cited by 24
Casanueva, E., Polo, E. M., Tejero, E., & Meza, C. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb26150.x · Cited by 22
VASE-encoded peptide modifies NCAM- and L1-mediated neurite outgrowth
Lahrtz, F., Horstkorte, R., Cremer, H., Schachner, M., & Montag, D. (1997) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19971001)50:1 · Cited by 21
Vitamins C and E and the Prevention of Preeclampsia
Briley, A. L., Poston, L., & Shennan, A. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmc061414 · Cited by 21
Vitamin C: working on the x-axis
Levine, M., & Eck, P. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28687 · Cited by 19
THE RECOMMENDED DIETARY ALLOWANCES FOR ASCORBIC ACID
Harper, A. E. (1975) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1975.tb29307.x · Cited by 18
Mazzuchin, A., Walton, R. J., & Thibert, R. J. (1971) · Biochemical Medicine · doi:10.1016/0006-2944(71)90082-2 · Cited by 17
Ontogenetic development of l-gulonolactone oxidase activity in several vertebrates
Jenness, R., Birney, E. C., Ayaz, K. L., & Buzzell, D. M. (1984) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(84)90162-7 · Cited by 16
Genomic and functional analysis of the sodium-dependent vitamin C transporter SLC23A1–SVCT1
Eck, P., Erichsen, H. C., Taylor, J. G., Corpe, C. P., Chanock, S. J., & Levine, M. (2007) · Genes & Nutrition · doi:10.1007/s12263-007-0040-7 · Cited by 15
Ascorbic acid synthesis by the mammalian fetus.
Cc, K., & Jd, K. (1986) · PubMed · Cited by 10
Prenatal Aspects of Ascorbic Acid Metabolism in the Albino Rat
Rosso, P., & Norkus, E. P. (1976) · Journal of Nutrition · doi:10.1093/jn/106.6.767 · Cited by 8
Flagged first, then by citations
Research works printed but not linked: 5
- Food and Nutrition Board, Panel on Dietary Antioxidants and Related Compounds. Vitamin C. In:Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids . Washington, DC: National Academy Press. 2000:95–185.
- Levine M, Katz A, Padayatty SJ. Vitamin C. In:Modern Nutrition in Health and Disease . Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Philadelphia, PA: Lippincott Williams and Wilkins. 2006:507–524.
- Kratzing, 1986, Int J Vitam Nutr Res., 56, 101
- Lind J.Treatise on Scurvy: A Bicentenary Volume Containing a Reprint of the First Edition of A Treatise of the Scurvy. Edinburgh, United Kingdom: Edinburgh University Press; 1951.
- Eisner, Kidney Int.
Cited by
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Du, J., Cullen, J. J., & Buettner, G. R. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.06.003 · Cited by 1,106
Vitamin C: The known and the unknown and Goldilocks
Padayatty, S., & Levine, M. (2016) · Oral Diseases · doi:10.1111/odi.12446 · Cited by 753
Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination
Doseděl, M., Jirkovský, E., Macáková, K., Krčmová, L., Javorská, L., Pourová, J., Mercolini, L., Remião, F., Nováková, L., Mladěnka, P., et al. (2021) · Nutrients · doi:10.3390/nu13020615 · Cited by 553
Targeting cancer vulnerabilities with high-dose vitamin C
Ngo, B., Van Riper, J. M., Cantley, L. C., & Yun, J. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0135-7 · Cited by 423
Carr, A. C., Rosengrave, P. C., Bayer, S., Chambers, S., Mehrtens, J., & Shaw, G. M. (2017) · Critical Care · doi:10.1186/s13054-017-1891-y · Cited by 413
Metadata
- Authors
- Corpe, C. P., Tu, H., Eck, P., Wang, J., Faulhaber-Walter, R., Schnermann, J., Margolis, S., Padayatty, S., Sun, H., Wang, Y., Nussbaum, R. L., Espey, M. G., & Levine, M.
- Affiliations
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- University of California, San Francisco (US)
- Corresponding author
- Levine, Mark
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2010-04-01
- Volume
- 120
- Issue
- 4
- Pages
- 1069-1083
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2847422
- OpenAlex
- W1982910588
- Cited by
- 162
- References
- 54
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 8 · 2023: 16 · 2022: 9 · 2021: 18 · 2020: 11 · 2019: 8 · 2018: 12 · 2017: 7 · 2016: 9 · 2015: 4 · 2014: 8 · 2013: 19 · 2012: 13
- FWCI
- 12.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institutes of Health (MD 20892)
- National Human Genome Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- vitamin C, SLC23A1, sodium-dependent vitamin C transporters, tubular reabsorption, perinatal survival, ascorbic acid biosynthesis, intestinal absorption, scurvy, knockout mice
- MeSH terms
- Absorption, Animals, Animals, Newborn, Ascorbic Acid, Female, Intestine, Small, Kidney, Liver, Mice, Inbred C57BL, Pregnancy, Polymorphism, Single Nucleotide, Symporters, Organic Anion Transporters, Sodium-Dependent, Mice, Perinatal Mortality, Sodium-Coupled Vitamin C Transporters
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