Title: γ-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo.
Authors: Le, Truc M; Jiang, Haiyan; Cunningham, Gary R; Magarik, Jordan A; Barge, William S; Cato, Marilyn C; Farina, Marcelo; Rocha, Joao B T; Milatovic, Dejan; Lee, Eunsook; Aschner, Michael; Summar, Marshall L
Published In Neurotoxicology, (2011 Oct)
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 (H(2)O(2))-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 H(2)O(2)-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.
PubMed ID: 21159318
MeSH Terms: Animals; Animals, Newborn; Astrocytes/drug effects; Astrocytes/metabolism*; Brain/drug effects; Brain/metabolism*; Cell Survival/drug effects; Cell Survival/physiology; Cells, Cultured; Dipeptides/pharmacology*; Glutathione/metabolism*; Mice; Mice, Inbred C57BL; Neurons/drug effects; Neurons/metabolism*; Neuroprotective Agents/pharmacology; Oxidative Stress/drug effects; Oxidative Stress/physiology*; Rats; Rats, Sprague-Dawley