A novel biological role of dehydroascorbic acid: Inhibition of Na(+)-dependent transport of ascorbic acid.
A U937 cell clone, in which low micromolar concentrations of ascorbic acid (AA) and dehydroascorbic acid (DHA) are taken up at identical rates, was used to investigate possible interactions between transport systems mediating cellular uptake of the two forms of the vitamin. Results obtained with different experimental approaches showed that DHA potently and reversibly inhibits AA uptake through Na(+)-AA cotransporters. Hence, a progressive increase in extracellular DHA concentrations in the presence of a fixed amount of AA caused an initial decrease in the net amount of vitamin C accumulated, and eventually, at higher levels, it caused an accumulation of the vitamin solely based on DHA uptake through hexose transporters. DHA-dependent inhibition of AA uptake was also detected in various other cell types. Taken together, our results provide evidence of a novel biological effect mediated by concentrations of DHA compatible with those produced at inflammatory sites.
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Urbino 61029, Italy.
Mara
M
Fiorani
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Urbino 61029, Italy.
Catia
C
Azzolini
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Urbino 61029, Italy.
Andrea
A
Guidarelli
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Urbino 61029, Italy.
Liana
L
Cerioni
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Urbino 61029, Italy. Electronic address: orazio.cantoni@uniurb.it.
Orazio
O
Cantoni
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000502:physiology*
D002352:Carrier Proteins; D012964:Sodium; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid
Ascorbic acid; Dehydroascorbic acid; Na(+)-dependent ascorbic acid transporters