Endogenous glutamate contributes to the maintenance of glutathione level under oxidative stress in isolated nerve terminals.
Exposure of isolated nerve terminals to hydrogen peroxide (25-500 microM) for 10 min produced a partially reversible decrease in the total and reduced glutathione level. No release and resynthesis of glutathione by the oxidant was involved in this effect. Loss of reduced glutathione was associated with elimination of H(2)O(2), which was very quick with >70% of the oxidant eliminated within 5 min. Recovery of both total and reduced glutathione was pronounced after 10 min when the majority of H(2)O(2) was eliminated. Previously we have reported that glutamate metabolism under oxidative stress contributes to the operation of the Krebs cycle, thus to the production of NAD(P)H [J. Neurosci. 20 (2000) 8972]. In the present study we addressed whether metabolism of endogenous glutamate plays a role in the maintenance of glutathione level in nerve terminals. Glutamine and beta-hydroxybutyrate (5mM), alternative metabolites in synaptosomes, were able to decrease the loss of total and reduced glutathione induced by hydrogen peroxide. Metabolic consumption of glutamate was reduced at the same time. In addition an increased demand on the glutathione system by the catalase inhibitor aminotriazole augmented the metabolic consumption of glutamate. It is concluded that under oxidative stress glutamate metabolism contributes to the maintenance of glutathione level, thus to the antioxidant capacity of nerve terminals.
Tretter
Laszlo
L
Neurochemical Group, Department of Medical Biochemistry, Semmelweis University of Medicine, P.O. Box 262, Budapest H-1444, Hungary.
Répássy
Regina
R
Adam-Vizi
Vera
V
D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D009411:Nerve Endings / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D005978:Glutathione