title: γ-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo.
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.
authors.affiliation: Division of Pediatric Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Truc M
authors.initials: TM
authors.lastname: Le
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cunningham
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Magarik
authors.forename: William S
authors.initials: WS
authors.lastname: Barge
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cato
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Joao B T
authors.initials: JB
authors.lastname: Rocha
authors.forename: Dejan
authors.initials: D
authors.lastname: Milatovic
authors.forename: Eunsook
authors.initials: E
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: Marshall L
authors.initials: ML
authors.lastname: Summar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004151:Dipeptides; D018696:Neuroprotective Agents; D005978:Glutathione; C017341:gamma-glutamylcysteine