title: Studies with low micromolar levels of ascorbic and dehydroascorbic acid fail to unravel a preferential route for vitamin C uptake and accumulation in U937 cells.
abstract: Mammalian cells accumulate vitamin C either as ascorbic acid (AA), via Na+-AA co-transport, or dehydroascorbic acid (DHA, the oxidation product of AA), via facilitative hexose transport. As the latter, unlike the former, is a high-capacity transport mechanism, cultured cells normally accumulate greater levels of vitamin C when exposed to increasing concentrations of DHA as compared with AA. We report herein similar results using the U937 cell clone used in our laboratory only under conditions in which DHA and AA are used at concentrations greater than 50-60 μm. Below 60 μm, i.e. at levels in which AA is normally found in most biological fluids, AA and DHA are in fact taken up with identical rates and kinetics. Consequently, extracellular oxidation of AA switches the mode of uptake with hardly any effect on the net amount of vitamin C accumulated. As a final note, under these conditions, neither AA nor DHA causes detectable toxicity or any change in the redox status of the cells, as assessed by the reduced glutathione/reduced pyridine nucleotide pool. These findings therefore imply that some cell types do not have a preferential route for vitamin C accumulation, and that the uptake mechanism is uniquely dependent on the extracellular availability of AA v. DHA.
authors.affiliation: Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino Carlo Bo, Via Saffi, 2, 61029 Urbino (PU), Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Azzolini
authors.forename: Mara
authors.initials: M
authors.lastname: Fiorani
authors.forename: Andrea
authors.initials: A
authors.lastname: Guidarelli
authors.forename: Orazio
authors.initials: O
authors.lastname: Cantoni
mesh_terms: D001205:Ascorbic Acid / Q000009:adverse effects / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival; D002999:Clone Cells; D003683:Dehydroascorbic Acid / Q000009:adverse effects / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D060347:Sodium-Coupled Vitamin C Transporters / Q000378:metabolism
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D060347:Sodium-Coupled Vitamin C Transporters; D009243:NAD; D009249:NADP; D005978:Glutathione; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid