Dehydroascorbic Acid Promotes Cell Death in Neurons Under Oxidative Stress: a Protective Role for Astrocytes.
Ascorbic acid (AA), the reduced form of vitamin C, is incorporated into neurons via the sodium ascorbate co-transporter SVCT2. However, this transporter is not expressed in astrocytes, which take up the oxidized form of vitamin C, dehydroascorbic acid (DHA), via the facilitative hexose transporter GLUT1. Therefore, neuron and astrocyte interactions are thought to mediate vitamin C recycling in the nervous system. Although astrocytes are essential for the antioxidant defense of neurons under oxidative stress, a condition in which a large amount of ROS is generated that may favor the extracellular oxidation of AA and the subsequent neuronal uptake of DHA via GLUT3, potentially increasing oxidative stress in neurons. This study analyzed the effects of oxidative stress and DHA uptake on neuronal cell death in vitro. Different analyses revealed the presence of the DHA transporters GLUT1 and GLUT3 in Neuro2a and HN33.11 cells and in cortical neurons. Kinetic analyses confirmed that all cells analyzed in this study possess functional GLUTs that take up 2-deoxyglucose and DHA. Thus, DHA promotes the death of stressed neuronal cells, which is reversed by incubating the cells with cytochalasin B, an inhibitor of DHA uptake by GLUT1 and GLUT3. Additionally, the presence of glial cells (U87 and astrocytes), which promote DHA recycling, reverses the observed cell death of stressed neurons. Taken together, these results indicate that DHA promotes the death of stressed neurons and that astrocytes are essential for the antioxidative defense of neurons. Thus, the astrocyte-neuron interaction may function as an essential mechanism for vitamin C recycling, participating in the antioxidative defense of the brain.
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Andrea
A
García-Krauss
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Luciano
L
Ferrada
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Allisson
A
Astuya
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Katterine
K
Salazar
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Pedro
P
Cisternas
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Fernando
F
Martínez
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile.
Eder
E
Ramírez
Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological Sciences, Concepcion University, Casilla 160-C, Concepción, Chile. frnualart@udec.cl.|Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile. frnualart@udec.cl.
Francisco
F
Nualart
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D003571:Cytochalasin B / Q000494:pharmacology; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D018696:Neuroprotective Agents; D003571:Cytochalasin B; D003847:Deoxyglucose; D003683:Dehydroascorbic Acid
Ascorbic acid; Astrocyte; Cell death; Dehydroascorbic acid; Neuron; Oxidative stress; Recycling