Elevation of mitochondrial glutathione by γ‐glutamylcysteine ethyl ester protects mitochondria against peroxynitrite‐induced oxidative stress

  title={Elevation of mitochondrial glutathione by $\gamma$‐glutamylcysteine ethyl ester protects mitochondria against peroxynitrite‐induced oxidative stress},
  author={Jennifer Drake and Rukhsana Sultana and Marina V. Aksenova and Vittorio Calabrese and David Allan Butterfield},
  journal={Journal of Neuroscience Research},
Mitochondria under oxidative stress are thought to play a key role in various neurodegenerative disorders by directing neurons to cell death. Protection by antioxidants against oxidative stress to mitochondria may prove to be beneficial in delaying onset or progression of these diseases. We have investigated the ability of γ‐glutamylcysteine ethyl ester (GCEE) to upregulate mitochondrial glutathione (GSH) in vivo or in vitro and protect against subsequent in vitro peroxynitrite (ONOO−) damage… 
γ‐glutamylcysteine ethyl ester‐induced up‐regulation of glutathione protects neurons against Aβ(1–42)‐mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease
It is suggested that GCEE up‐regulates cellular GSH levels which, in turn, protects neurons against protein oxidation, loss of mitochondrial function, and DNA fragmentation induced by Aβ(1–42).
Mitochondrial isocitrate dehydrogenase protects human neuroblastoma SH‐SY5Y cells against oxidative stress
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Protective Effect of Carnosine During Nitrosative Stress in Astroglial Cell Cultures
Carnosine protected against nitric oxide-induced impairment of mitochondrial function and was associated with decreased formation of oxidatively modified proteins and with decreased up-regulation oxidative stress-responsive genes, such as Hsp32, Hsp70 and mt-SOD.
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GGC effectively attenuated LPS-induced ROS and stress granule formation, while significantly increasing intracellular glutathione levels and improving epithelial cell barrier integrity, indicating that GGC has therapeutic potential for treatment and prevention of oxidative stress related damage to airways in Cystic Fibrosis.
Original Contribution In vivo protection of synaptosomes from oxidative stress mediated by Fe 2+ /H 2 O 2 or 2,2-azobis-(2-amidinopropane) dihydrochloride by the glutathione mimetic tricyclodecan-9-yl-xanthogenate
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Elevation of brain glutathione by γ‐glutamylcysteine ethyl ester protects against peroxynitrite‐induced oxidative stress
The experiments suggest that GCEE is effective in increasing brain GSH levels and may potentially play an important therapeutic role in attenuating oxidative stress in neurodegenerative diseases associated with oxidative stress such as Alzheimer disease.
5-Aminosalicylic Acid Protection against Oxidative Damage to Synaptosomal Membranes by Alkoxyl Radicals In Vitro
Results are consistent with the notion of antioxidant protection against free radical induced oxidative stress in synaptosomal membrane system by this agent.
Peroxynitrite‐Induced Alterations in Synaptosomal Membrane Proteins
Investigation of damage to brain neocortical synaptosomal membrane proteins and the oxidation‐sensitive enzyme glutamine synthetase caused by exposure to ONOO shows that ONOO‐ can oxidatively modify both membranous and cytosolic proteins, affecting both their physical and chemical nature.
Inhibition of mitochondrial electron transport by peroxynitrite.
It is reported that peroxynitrite exposure to rat heart mitochondria resulted in significant inactivation of electron carriers such as succinate dehydrogenase and NADH dehydrogenases as well as the mitochondrial ATPase, indicating that mitochondria may constitute a key intracellular loci for the toxic effects of peroxysitrite under the various pathological conditions in which each appears to play a contributory role.
Mitochondrial glutathione: importance and transport.
The elucidation of the mechanisms whereby ethanol leads to its impaired activity may provide important clues as to its function and mechanism of action, which in turn may be useful toward the definitive characterization and identification of this important carrier.
Prevention of Mitochondrial Oxidative Damage Using Targeted Antioxidants
Using mitochondrial‐targeted antioxidants that selectively block mitochondrial oxidative damage and prevent some types of cell death may help investigations of the role of mitochondria oxidative damage in animal models of aging.
Effect of Exogenous and Endogenous Antioxidants on 3‐Nitropionic Acid‐Inducedin vivo Oxidative Stress and Striatal Lesions
Data suggest oxidative damage is a prerequisite for striatal lesion formation and that antioxidant treatment may be a useful therapeutic strategy against 3‐NP neurotoxicity and perhaps against HD as well.
Mitochondrial glutathione oxidation correlates with age‐associated oxidative damage to mitochondrial DNA
  • J. Asuncion, A. Millán, J. Viña
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1996
The role of glutathione in the protection against free radical damage that occurs upon aging is underscored and a direct relationship between mtDNA damage and mitochondrial glutATHione oxidation is found.
Ca2+-independent permeabilization of the inner mitochondrial membrane by peroxynitrite is mediated by membrane protein thiol cross-linking and lipid peroxidation.
The results support the idea that under experimental conditions peroxynitrite causes mitochondrial structural and functional alterations by Ca2+-independent mechanisms through lipid peroxidation and protein sulfhydryl oxidation.