These authors contributed equally to this work.
The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism
Article first published online: 19 FEB 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 129, Issue 4, pages 663–671, May 2014
How to Cite
J. Neurochem. (2014) 129, 663–671.
- Issue published online: 23 APR 2014
- Article first published online: 19 FEB 2014
- Accepted manuscript online: 25 JAN 2014 03:45AM EST
- Manuscript Accepted: 9 JAN 2014
- Manuscript Revised: 6 JAN 2014
- Manuscript Received: 6 SEP 2013
- FONDECYT. Grant Number: 1100396
- Ministerio de Economía y Competitividad. Grant Number: SAF2010-20008
- European Regional Development Fund
- Instituto de Salud Carlos III. Grant Number: RD12/0043/0021
- Junta de Castilla y Leon. Grant Number: SA112A12-2
- DIUC. Grant Number: 211031109-1.0
- oxidative stress;
- pentose-phosphate pathway
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.
We proposed that the ascorbic acid (AA) taken up by neurons is rapidly oxidized to dehydroascorbic acid (DHA), which inhibits glycolysis and activates the pentose phosphate pathway (PPP), consequently producing NADPH, a critical antioxidant in the recycling of oxidized glutathione (GSSG). In these metabolic conditions, neurons increase lactate uptake, probably using it as an energy source. This data supported the idea that DHA could play a critical role in the modulation of energy metabolism in neurons.