Exp Mol Med.  2002 Dec;34(6):419-425.

Effects of glutamate on dehydroascorbate uptake and Its enhanced vulnerability to the peroxidation in cerebral cortical slices

• Song JH
• Shin SH
• Chung IM

Abstract

Pro-oxidant properties of ascorbate have been studied with uses of brain tissues and neuronal cells. Here we address potential mechanism of ascorbate coupling with glutamate to generate oxidative stress, and the role which oxidized ascorbate (dehydroascorbate) transport plays in oxidative neuronal injury. Ascorbate in neurones can be depleted by adding glutamate in culture medium since endogenous ascorbate can be exchanged with glutamate, which enhances ascorbate/ dehydroascorbate transport by depleting ascorbate in the neurons with the glutamate-heteroexchange. However, ascorbate is known readily being oxidized to dehydroascorbate in the medium. Glutamate enhanced the dehydroascorbate uptake by cells via a glucose transporter (GLUT) from extracellular region, and cytosolic dehydroascorbate enhanced lipid peroxide production and reduced glutathione (GSH) concentrations. Iso-ascorbate, the epimer of ascorbate was ineffective in generating the oxidative stress. These observations support the current concept that the high rates of dehydroascorbate transport via a GLUT after the release of ascorbate by glutamate leads to peroxidation, the role of glutamate on ascorbate/ dehydroascorbate recycling being critical to induce neuronal death via an oxidative stress in the brain injury.

Keyword

ascorbate; glucose transporter; glutathione; lipid peroxide; neuronal death; oxidative stress

MeSH Terms

Animals
Ascorbic Acid/analogs & derivatives/pharmacology
Biological Transport/drug effects
Cerebral Cortex/*drug effects/*metabolism
Cytochalasin B/pharmacology
Dehydroascorbic Acid/*metabolism
Glutamic Acid/*pharmacology
Glutathione/metabolism
In Vitro
Lipid Peroxidation/*drug effects
Male
Oxidation-Reduction/drug effects
Oxidative Stress/drug effects
Rats
Rats, Sprague-Dawley
Thiobarbituric Acid Reactive Substances/metabolism