The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism.
Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time- and dose-dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes.
Laboratorio de Neurobiología, Departamento de Biología Celular, Centro de Microscopía Avanzada CMA BIOBIO, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Pedro
P
Cisternas
Carmen
C
Silva-Alvarez
Fernando
F
Martínez
Emilio
E
Fernandez
Luciano
L
Ferrada
Karina
K
Oyarce
Katterine
K
Salazar
Juan P
JP
Bolaños
Francisco
F
Nualart
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D002478:Cells, Cultured; D003683:Dehydroascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D060347:Sodium-Coupled Vitamin C Transporters / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007773:Lactates; C555167:Slc23a2 protein, rat; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; D005947:Glucose; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid
glutathione; glycolysis; lactate; oxidative stress; pentose-phosphate pathway