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J. Biol. Chem., Vol. 278, Issue 11, 9035-9041, March 14, 2003
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From the Human cells acquire vitamin C using two different
transporter systems, the sodium-ascorbic acid co-transporters with
specificity for ascorbic acid, and the facilitative glucose
transporters with specificity for dehydroascorbic acid. There is no
information on the mechanism of vitamin C transport across the
intestinal barrier, a step that determines the bioavailability of
vitamin C in humans. We used the colon carcinoma cell line CaCo-2 as an in vitro model for vitamin C transport in enterocyte-like
cells. The results of transport kinetics, sodium dependence, inhibition studies, and reverse transcriptase-PCR analysis indicated that CaCo-2
cells express the sodium-ascorbate co-transporters SVCT1 and SVCT2, the
dehydroascorbic acid transporters GLUT1 and GLUT3, and a third
dehydroascorbic acid transporter with properties expected for GLUT2.
Analysis by real time quantitative PCR revealed that the post-confluent
differentiation of CaCo-2 cells was accompanied by a marked increase
(4-fold) in the steady-state level of SVCT1 mRNA, without changes
in SVCT2 mRNA levels. Functional studies revealed that the
differentiated cells expressed only one functional ascorbic acid
transporter having properties expected for SVCT1, and transported
ascorbic acid with a Vmax that was increased at least 2-fold compared with pre-confluent cells. Moreover,
post-confluent Caco-2 cells growing as monolayers in permeable filter
inserts showed selective sorting of SVCT1 to the apical membrane
compartment, without functional evidence for the expression of SVCT2.
The identification of SVCT1 as the transporter that allows vectorial
uptake of ascorbic acid in differentiated CaCo-2 cells has a direct
impact on our understanding of the mechanism for vitamin C transport
across the intestinal barrier.
Up-regulation and Polarized Expression of the Sodium-Ascorbic
Acid Transporter SVCT1 in Post-confluent Differentiated CaCo-2
Cells*
§,,,¶,
,,,
Departamento de
Fisiopatología, the ** Departamento de
Histología y Embriología, Facultad de Ciencias
Biológicas, Universidad de Concepción, Barrio Universitario
S/N, Concepción, Chile, the § Departamento de
Biología Molecular, Facultad de Medicina, Universidad
Católica de la Santísima Concepción, Alonso de
Ribera 2850, Concepción, Chile, ¶ Instituto de
Bioquímica, Facultad de Ciencias, Universidad Austral de Chile,
Campus Isla Teja, Valdivia, Chile, and Institut of Clinical
Chemistry, Faculty of Medicine, University of Ulm, 8907 Ulm, Germany
*
This work was supported in part by Grants 3990007, 3000024, 1990333, and 1020451 from FONDECYT, Chile, and grant 201034006-1.4 from
the Dirección de Investigación, Universidad de
Concepción, Concepción, Chile.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 56-41-203817;
Fax: 56-41-216558; E-mail: juvera@udec.cl.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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