Vitamin C uptake and recycling among normal and tumor cells from the central nervous system

Allisson Astuya, Teresa Caprile, Maite Castro, Katterine Salazar, María De Los Angeles García, Karin Reinicke, Federico Rodríguez, Juan Carlos Vera, Carola Millán, Viviana Ulloa, Marcela Low, Fernando Martínez, Francisco Nualart

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Specialized cells transport vitamin C in its reduced form using sodium-dependent cotransporters (SVCT1 and SVCT2). Additionally, different cells transport the oxidized form of vitamin C, dehydroascorbic acid, through glucose transporters (GLUTs). We have proposed recently a model for vitamin C uptake that resolves the apparent contradiction that although only ascorbic acid is detectable in vivo, there are cells that transport only dehydroascorbic acid. We carried out a detailed kinetic analysis to compare the mechanisms of vitamin C uptake in normal human melanocytes, neurons isolated from brain cortex, hypothalamic ependymal-glial cells, and astrocytes. Uptake of ascorbic acid was also analyzed in the human oligodendroglioma cell line TC620, in human choroid plexus papilloma cells (HCPPC-1), and in the neuroblastoma cell line Neuro-2a. Melanocytes were used to carry out a detailed analysis of vitamin C uptake. Analysis of the transport data by the Lineweaver-Burk plot revealed the presence of one functional component (Km 20 μM) involved in ascorbic acid transport by melanocytes. Vitamin C sodium-dependent saturable uptake was also observed in neurons and hypothalamic tanycytes. We confirmed SVCT2 expression in neurons by in situ hybridization; however, SVCT2 expression was not detected in astrocytes in situ. Functional data indicate that astrocytes transport mainly dehydroascorbic acid, using the glucose transporter GLUT1. Our functional uptake analyses support the hypothesis that astrocytes are involved in vitamin C recycling in the nervous system. This recycling model may work as an efficient system for the salvage of vitamin C by avoiding the hydrolysis of dehydroascorbic acid produced by antioxidative protection.

Original languageEnglish
Pages (from-to)146-156
Number of pages11
JournalJournal of Neuroscience Research
Volume79
Issue number1-2
DOIs
StatePublished - 15 Jan 2005
Externally publishedYes

Keywords

  • GLUT
  • Neuron-astrocyte interaction
  • SVCT2
  • Tumor cells
  • Vitamin C

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