The Oxidized Form of Vitamin C, Dehydroascorbic Acid, Regulates Neuronal Energy Metabolism

J Neurochem. 2014 May;129(4):663-71. doi: 10.1111/jnc.12663. Epub 2014 Feb 19.

Abstract

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.

Keywords: glutathione; glycolysis; lactate; oxidative stress; pentose-phosphate pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / pharmacology
  • Biological Transport
  • Cells, Cultured
  • Dehydroascorbic Acid / metabolism
  • Dehydroascorbic Acid / pharmacology*
  • Energy Metabolism / drug effects*
  • Glucose / metabolism
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / metabolism
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione / metabolism
  • Glycolysis / drug effects
  • Lactates / metabolism
  • Models, Neurological
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oxidation-Reduction
  • Pentose Phosphate Pathway / drug effects
  • Primary Cell Culture
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Coupled Vitamin C Transporters / metabolism

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Lactates
  • Slc23a2 protein, rat
  • Slc2a1 protein, rat
  • Slc2a3 protein, rat
  • Sodium-Coupled Vitamin C Transporters
  • Glucosephosphate Dehydrogenase
  • Glutathione
  • Glucose
  • Ascorbic Acid
  • Dehydroascorbic Acid