Cellular pathways for transport and efflux of ascorbate and dehydroascorbate

Corti, Alessandro; Casini, Alessandro F.; Pompella, Alfonso

doi:10.1016/j.abb.2010.05.014

Cited by 193Vitamin C and Antioxidants ResearchAmino Acid Enzymes and MetabolismAntioxidant Activity and Oxidative Stress

Cellular pathways for transport and efflux of ascorbate and dehydroascorbate

Corti, Alessandro, Casini, Alessandro F., Pompella, Alfonso·2010·Archives of Biochemistry and Biophysics

DOI 10.1016/j.abb.2010.05.014

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Abstract

The mechanisms allowing the cellular transport of ascorbic acid represent a primary aspect for the understanding of the roles played by this vitamin in pathophysiology. Considerable research effort has been spent in the field, on several animal models and different cell types. Several mechanisms have been described to date, mediating the movements of different redox forms of ascorbic acid across cell membranes. Vitamin C can enter cells both in its reduced and oxidized form, ascorbic acid (AA) and dehydroascorbate (DHA), utilizing respectively sodium-dependent transporters (SVCT) or glucose transporters (GLUT). Modulation of SVCT expression and function has been described by cytokines, steroids and post-translational protein modification. Cellular uptake of DHA is followed by its intracellular reduction to AA by several enzymatic and non-enzymatic systems. Efflux of vitamin C has been also described in a number of cell types and different pathophysiological functions were proposed for this phenomenon, in dependence of the cell model studied. Cellular efflux of AA is mediated through volume-sensitive (VSOAC) and Ca(2+)-dependent anion channels, gap-junction hemichannels, exocytosis of secretory vesicles and possibly through homo- and hetero-exchange systems at the plasma membrane level. Altogether, available data suggest that cellular efflux of ascorbic acid - besides its uptake - should be taken into account when evaluating the cellular homeostasis and functions of this important vitamin.

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Cancer cells with high GLUT1, rather than sodium-dependent vitamin C transporters, take up ascorbate only as DHA in culture and in animals.
“cancer cells with high GLUT1 but not sodium-dependent vitamin C transporters exclusively take up ascorbate in the form of DHA both in vitro or in vivo6,8,47,53.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [6]

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Physiology of Astroglia
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SOD Therapeutics: Latest Insights into Their Structure-Activity Relationships and Impact on the Cellular Redox-Based Signaling Pathways
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Ascorbate as a co-factor for Fe- and 2-oxoglutarate dependent dioxygenases: Physiological activity in tumor growth and progression
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Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders
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Does Vitamin C Deficiency Affect Cognitive Development and Function?
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Deep Learning for Voltammetric Sensing in a Living Animal Brain
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Red Blood Cell Metabolism In Vivo and In Vitro
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Novel roles of ascorbate in plants: induction of cytosolic Ca2+ signals and efflux from cells via anion channels
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Nanoparticles as a novel delivery system for vitamin C administration in aquaculture
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The redox interplay between nitrite and nitric oxide: From the gut to the brain
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Voss, G. T., Gularte, M. S., Vogt, A. G., Giongo, J. L., Vaucher, R. D. A., Echenique, J. V. Z., Soares, M. P., Luchese, C., Wilhelm, E. A., & Fajardo, A. R. (2018) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2018.10.009 · Cited by 90 · see citing works
Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts
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High-Dose Vitamin C for Cancer Therapy
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The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism
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Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator
Thiabaud, G., McCall, R., He, G., Arambula, J. F., Siddik, Z. H., & Sessler, J. L. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201604236 · Cited by 71 · see citing works
Electrochemical Monitoring of Propagative Fluctuation of Ascorbate in the Live Rat Brain during Spreading Depolarization
Xiao, T., Wang, Y., Wei, H., Yu, P., Jiang, Y. Y., & Mao, L. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201901035 · Cited by 71 · see citing works
Subcellular compartmentation of ascorbate and its variation in disease states
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Cell Microenvironment-Controlled Antitumor Drug Releasing-Nanomicelles for GLUT1-Targeting Hepatocellular Carcinoma Therapy
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Intravenous Vitamin C in the treatment of shingles: Results of a multicenter prospective cohort study
Schencking, M., Vollbracht, C., Weiß, G., Lebert, J., Biller, A., Goyvaerts, B., & Kraft, K. (2012) · Medical Science Monitor · doi:10.12659/msm.882621 · Cited by 65 · see citing works
Local Vitamin-C Injection Reduced Tendon Adhesion in a Chicken Model of Flexor Digitorum Profundus Tendon Injury
Hung, L., Fu, S., Lee, Y.-W., Mok, T. Y., & Chan, K.-M. (2013) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.k.00988 · Cited by 63 · see citing works
The effect of oxidative and reductive stress on semen parameters and functions of physiologically normal human spermatozoa
Selvam, M. K. P., Agarwal, A. K., Henkel, R., Finelli, R., Robert, K. A., Iovine, C., & Baskaran, S. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.03.008 · Cited by 60 · see citing works
Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile
Pires, A. S., Marques, C. R., Encarnação, J. C., Abrantes, A. M., Mamede, A. C., Laranjo, M., Gonçalves, A. C., Sarmento‐Ribeiro, A. B., & Botelho, M. F. (2016) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2016.04.001 · Cited by 57 · see citing works
Dehydroascorbic Acid Promotes Cell Death in Neurons Under Oxidative Stress: a Protective Role for Astrocytes
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Vitamin C Transporters in Cancer: Current Understanding and Gaps in Knowledge
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Ascorbic Acid: An Old Player with a Broad Impact on Body Physiology Including Oxidative Stress Suppression and Immunomodulation: A Review
Pohanka, M., Pejchal, J., Snopková, S., Havlíčková, K., Karasová, J. Ž., Boštík, P., & Pikula, J. (2011) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955712798868986 · Cited by 52 · see citing works
Functionalized Nanoscale Micelles with Brain Targeting Ability and Intercellular Microenvironment Biosensitivity for Anti‐Intracranial Infection Applications
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Antioxidant Delivery Pathways in the Anterior Eye
Umapathy, A., Donaldson, P. J., & Lim, J. C.-H. (2013) · BioMed Research International · doi:10.1155/2013/207250 · Cited by 49 · see citing works
Rapid, sensitive and simultaneous determination of ascorbic and uric acids in human plasma by ion-exclusion HPLC-UV
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Selective Amperometric Recording of Endogenous Ascorbate Secretion from a Single Rat Adrenal Chromaffin Cell with Pretreated Carbon Fiber Microelectrodes
Wang, K., Xiao, T., Yue, Q., Wu, F., Yu, P., & Mao, L. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b02508 · Cited by 45 · see citing works
Glycation of bovine serum albumin by ascorbate in vitro: Possible contribution of the ascorbyl radical?
Sadowska‐Bartosz, I., Stefaniuk, I., Galiniak, S., & Bartosz, G. (2015) · Redox Biology · doi:10.1016/j.redox.2015.06.017 · Cited by 46 · see citing works
The pharmacology of vitamin C
Lykkesfeldt, J., Carr, A. C., & Tveden‐Nyborg, P. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100043 · Cited by 44 · see citing works
Sodium l-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin
Hinek, A., Kim, H. J., Wang, Y., Wang, A., & Mitts, T. F. (2014) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2014.05.011 · Cited by 41 · see citing works
Lipid bands of approx. 1740 cm−1 as spectral biomarkers and image of tissue oxidative stress
Pielesz, A., Biniaś, D., Waksmańska, W., & Bobiński, R. (2022) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2022.121926 · Cited by 41 · see citing works
A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Batinic̈‐Haberle, I., Rajić, Z., & Benov, L. (2011) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/187152011795677562 · Cited by 40 · see citing works
Nutraceuticals in the Prevention of Viral Infections, including COVID-19, among the Pediatric Population: A Review of the Literature
Parisi, G. F., Carota, G., Castruccio Castracani, C., Spampinato, M., Manti, S., Papale, M., Di Rosa, M., Barbagallo, I., & Leonardi, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052465 · Cited by 43 · see citing works
Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats
Picklo, M. J., & Thyfault, J. P. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2014-0302 · Cited by 38 · see citing works
Striae Distensae: In Vitro Study and Assessment of Combined Treatment With Sodium Ascorbate and Platelet-Rich Plasma on Fibroblasts
Padula, S. L., Hersant, B., Pizza, C., Chesné, C., Jamin, A., Mosbah, I. B., Errico, C., D’Andrea, F., Rega, U., Persichetti, P., et al. (2021) · Aesthetic Plastic Surgery · doi:10.1007/s00266-020-02100-7 · Cited by 37 · see citing works
The Influence of Manganese and Glutamine Intake on Antioxidants and Neurotransmitter Amino Acids Levels in Rats’ Brain
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A targeting theranostics nanomedicine as an alternative approach for hyperthermia perfusion
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A Versatile Theranostic Platform for Colorectal Cancer Peritoneal Metastases: Real‐Time Tumor‐Tracking and Photothermal‐Enhanced Chemotherapy
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Mitochondrial Uptake and Accumulation of Vitamin C: What Can We Learn from Cell Culture Studies?
Cantoni, O., Guidarelli, A., & Fiorani, M. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7253 · Cited by 33 · see citing works
New Perspectives on Iron Uptake in Eukaryotes
Sherman, H. G., Jovanovic, C., Stolnik, S., Baronian, K. H. R., Downard, A. J., & Rawson, F. J. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00097 · Cited by 31 · see citing works
GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy
Guo, Q., Li, C., Zhou, W., Chen, X., Zhang, Y., Lü, Y., Zhang, Y., Chen, Q., Liang, D., Sun, T., et al. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.01.012 · Cited by 32 · see citing works
Falkenbergia rufolanosa polysaccharide – Poly(vinyl alcohol) composite films: A promising wound healing agent against dermal laser burns in rats
Feki, A., Bardaa, S., Hajji, S., Ktari, N., Hamdi, M., Chabchoub, N., Kallel, R., Boudawara, T. S., Nasri, M., & Amara, I. B. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.09.173 · Cited by 32 · see citing works
Expression of hypoxia inducible factor 1α and 2α and its association with vitamin C level in thyroid lesions
Jóźwiak, P., Ciesielski, P., Zaczek, A., Lipińska, A., Pomorski, L., Wieczorek, M., Bryś, M., Forma, E., & Krześlak, A. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0388-y · Cited by 31 · see citing works
Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma
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The role of topically applied l -ascorbic acid in ex-vivo examination of burn-injured human skin
Pielesz, A., Biniaś, D., Bobiński, R., Sarna, E., Paluch, J., & Waksmańska, W. (2017) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2017.05.055 · Cited by 31 · see citing works
Effect of dietary vitamin C level during early larval stages in Senegalese sole (Solea senegalensis)
Jiménez-Fernández, E., Ponce, M., Rodriguez‐Rúa, A., Zuasti, E., Manchado, M., & Fernández‐Díaz, C. (2015) · Aquaculture · doi:10.1016/j.aquaculture.2015.03.013 · Cited by 31 · see citing works
Multicopper oxidase-1 orthologs from diverse insect species have ascorbate oxidase activity
Peng, Z., Dittmer, N. T., Lang, M., Brummett, L. M., Braun, C. L., Davis, L. C., Kanost, M. R., & Gorman, M. J. (2015) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2015.02.005 · Cited by 30 · see citing works
Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?
Kouakanou, L., Peters, C., Brown, C. E., Kabelitz, D., & Wang, L. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.765906 · Cited by 30 · see citing works
Bioavailability of vitamin C from mashed potatoes and potato chips after oral administration in healthy Japanese men
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Authors: Corti, A., Casini, A. F., & Pompella, A.
Affiliations: University of Pisa (IT)
Corresponding author: Corti, Alessandro
ORCID: Corti, Alessandro
Casini, Alessandro F.
Venue: Archives of Biochemistry and Biophysics
Publisher: Elsevier BV
Published: 2010-08
Volume: 500
Issue: 2
Pages: 107-115
ISSN: 0003-9861 (ISSN-L)
DOI: 10.1016/j.abb.2010.05.014
OpenAlex: W2024573050
Cited by: 193
References: 193
Citations by year: 2026: 3 · 2025: 7 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 17 · 2020: 14 · 2019: 17 · 2018: 15 · 2017: 16 · 2016: 10 · 2015: 20 · 2014: 17 · 2013: 14 · 2012: 16
FWCI: 1.47
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Archives of Biochemistry and Biophysics (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders: Istituto Toscano Tumori
Ministero dell'Università e della Ricerca
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords: vitamin C, dehydroascorbic acid, vitamin C transport, sodium-dependent vitamin C transporters, glucose transporters, gap junction hemichannels, exocytosis, intracellular reduction, post-translational modification
MeSH terms: Animals, Ascorbic Acid, Biological Transport, Active, Cell Membrane, Dehydroascorbic Acid, Humans, Ion Channels, Models, Biological, Neoplasms, Oxidation-Reduction, Symporters, Organic Anion Transporters, Sodium-Dependent, Glucose Transport Proteins, Facilitative

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Cellular pathways for transport and efflux of ascorbate and dehydroascorbate

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