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Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation

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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.

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Abbreviations

4-CIN:

α-cyano-4-hydroxycinnamate

CytB:

cytochalasin B

DHA:

dehydroascorbic acid

DOG:

deoxyglucose

DTT:

dithiothreitol

GLUT:

glucose transporter

MCT:

monocarboxylate transporter

Oua:

ouabain

SVCT:

sodium vitamin C transporter

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Acknowledgments

This work was supported in part by Chilean grants FONDECYT 1060135 and ACT-02 Conicyt-PBCT.

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Authors and Affiliations

  1. Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile

    Maite A. Castro, Constanza Angulo, Sebastián Brauchi & Ilona I. Concha

  2. Laboratorio de Neurobiología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160C, Concepción, Chile

    Francisco Nualart

  3. Laboratorio de Señalización Celular, Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Casilla 547, Valdivia, Chile

    Ilona I. Concha

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  1. Maite A. Castro
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  2. Constanza Angulo
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Correspondence to Francisco Nualart or Ilona I. Concha.

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Castro, M.A., Angulo, C., Brauchi, S. et al. Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation. Pflugers Arch - Eur J Physiol 457, 519–528 (2008). https://doi.org/10.1007/s00424-008-0526-1

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