γ-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo

Truc M. Le, Haiyan Jiang, Gary R. Cunningham, Jordan A. Magarik, William S. Barge, Marilyn C. Cato, Marcelo Farina, Joao B T Rocha, Dejan Milatovic, Eunsook Lee, Michael Aschner, Marshall L. Summar

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

γ-Glutamylcysteine (γ-GC) is an intermediate molecule of the glutathione (GSH) synthesis pathway. In the present study, we tested the hypothesis that γ-GC pretreatment in cultured astrocytes and neurons protects against hydrogen peroxide (H2O2)-induced oxidative injury. We demonstrate that pretreatment with γ-GC increases the ratio of reduced:oxidized GSH levels in both neurons and astrocytes and increases total GSH levels in neurons. In addition, γ-GC pretreatment decreases isoprostane formation both in neurons and astrocytes, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation in astrocytes in response to H2O2-induced oxidative stress. Furthermore, GSH and isoprostane levels significantly correlate with increased neuron and astrocyte viability in cells pretreated with γ-GC. Finally, we demonstrate that administration of a single intravenous injection of γ-GC to mice significantly increases GSH levels in the brain, heart, lungs, liver, and in muscle tissues in vivo. These results support a potential therapeutic role for γ-GC in the reduction of oxidant stress-induced damage in tissues including the brain.

Original languageEnglish (US)
Pages (from-to)518-525
Number of pages8
JournalNeuroToxicology
Volume32
Issue number5
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Astrocyte
  • Glutathione
  • Neuron
  • Reactive oxygen species
  • γ-Glutamylcysteine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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  • Cite this

    Le, T. M., Jiang, H., Cunningham, G. R., Magarik, J. A., Barge, W. S., Cato, M. C., Farina, M., Rocha, J. B. T., Milatovic, D., Lee, E., Aschner, M., & Summar, M. L. (2011). γ-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo. NeuroToxicology, 32(5), 518-525. https://doi.org/10.1016/j.neuro.2010.11.008