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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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Ascorbic acid: Chemistry, biology and the treatment of cancer
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
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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
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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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