title: Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation.
abstract: In this paper, we present a novel function for ascorbic acid. Ascorbic acid is an important water-soluble antioxidant and cofactor in various enzyme systems. We have previously demonstrated that an increase in neuronal intracellular ascorbic acid is able to inhibit glucose transport in cortical and hippocampal neurons. Because of the presence of sodium-dependent vitamin C transporters, ascorbic acid is highly concentrated in brain, testis, lung, and adrenal glands. In this work, we explored how ascorbic acid affects glucose and lactate uptake in neuronal and non-neuronal cells. Using immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, the expression of glucose and ascorbic acid transporters in non-neuronal cells was studied. Like neurons, HEK293 cells expressed GLUT1, GLUT3, and SVCT2. With radioisotope-based methods, only intracellular ascorbic acid, but not extracellular, inhibits 2-deoxyglucose transport in HEK293 cells. As monocarboxylates such as pyruvate and lactate, are important metabolic sources, we analyzed the ascorbic acid effect on lactate transport in cultured neurons and HEK293 cells. Intracellular ascorbic acid was able to stimulate lactate transport in both cell types. Extracellular ascorbic acid did not affect this transport. Our data show that ascorbic acid inhibits glucose transport and stimulates lactate transport in neuronal and non-neuronal cells. Mammalian cells frequently present functional glucose and monocarboxylate transporters, and we describe here a general effect in which ascorbic acid functions like a glucose/monocarboxylate uptake switch in tissues expressing ascorbic acid transporters.
authors.affiliation: Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Maite A
authors.initials: MA
authors.lastname: Castro
authors.forename: Constanza
authors.initials: C
authors.lastname: Angulo
authors.forename: Sebastián
authors.initials: S
authors.lastname: Brauchi
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
authors.forename: Ilona I
authors.initials: II
authors.lastname: Concha
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000819:agonists / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000819:agonists / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; C555163:SLC23A2 protein, human; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C555167:Slc23a2 protein, rat; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D019344:Lactic Acid; D003847:Deoxyglucose; D006593:Hexokinase; D005947:Glucose; D001205:Ascorbic Acid