Chemical Transport Knockout for Oxidized Vitamin C, Dehydroascorbic Acid, Reveals Its Functions in vivo
Open accessAbstract
Despite its transport by glucose transporters (GLUTs) in vitro , it is unknown whether dehydroascorbic acid (oxidized vitamin C, DHA) has any in vivo function. To investigate, we created a chemical transport knockout model using the vitamin C analog 6-bromo-ascorbate. This analog is transported on sodium-dependent vitamin C transporters but its oxidized form, 6-bromo-dehydroascorbic acid, is not transported by GLUTs. Mice (gulo −/− ) unable to synthesize ascorbate (vitamin C) were raised on 6-bromo-ascorbate. Despite normal survival, centrifugation of blood produced hemolysis secondary to near absence of red blood cell (RBC) ascorbate/6-bromo-ascorbate. Key findings with clinical implications were that RBCs in vitro transported dehydroascorbic acid but not bromo-dehydroascorbic acid; RBC ascorbate in vivo was obtained only via DHA transport; ascorbate via DHA transport in vivo was necessary for RBC structural integrity; and internal RBC ascorbate was essential to maintain ascorbate plasma concentrations in vitro / in vivo .
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That conversion lowers intracellular antioxidants and raises endogenous ROS.
“This reduction depletes intracellular antioxidants and increases endogenous levels of ROS47,50.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [50]
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References 57 · Cited by 35
- Authors
- Tu, H., Wang, Y., Li, H., Brinster, L. R., & Levine, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Levine, Mark
- Venue
- EBioMedicine
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 23
- Pages
- 125-135
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC5605377
- OpenAlex
- W2748168610
- Cited by
- 35
- References
- 57
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 4
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EBioMedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health (1Z1ADK053218-10)
- NIH (1ZIADK053218-10)
- 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 › Molecular Biology › Redox biology and oxidative stress
- Keywords
- dehydroascorbic acid, sodium-dependent vitamin C transporters, glucose transporters, hemolysis
- MeSH terms
- Animals, Ascorbic Acid, Biological Transport, Cell Membrane, Dehydroascorbic Acid, Erythrocytes, Glucose, Hemolysis, Oxidation-Reduction, Oxidoreductases, Phenotype, Sugar Acids, Mice, Knockout, Mice, Gene Knockout Techniques
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