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Title:
γ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor | Nature Communications
Description:
Reactive oxygen species regulate redox-signaling processes, but in excess they can cause cell damage, hence underlying the aetiology of several neurological diseases. Through its ability to down modulate reactive oxygen species, glutathione is considered an essential thiol-antioxidant derivative, yet under certain circumstances it is dispensable for cell growth and redox control. Here we show, by directing the biosynthesis of γ-glutamylcysteine—the immediate glutathione precursor—to mitochondria, that it efficiently detoxifies hydrogen peroxide and superoxide anion, regardless of cellular glutathione concentrations. Knocking down glutathione peroxidase-1 drastically increases superoxide anion in cells synthesizing mitochondrial γ-glutamylcysteine. In vitro, γ-glutamylcysteine is as efficient as glutathione in disposing of hydrogen peroxide by glutathione peroxidase-1. In primary neurons, endogenously synthesized γ-glutamylcysteine fully prevents apoptotic death in several neurotoxic paradigms and, in an in vivo mouse model of neurodegeneration, γ-glutamylcysteine protects against neuronal loss and motor impairment. Thus, γ-glutamylcysteine takes over the antioxidant and neuroprotective functions of glutathione by acting as glutathione peroxidase-1 cofactor. Glutathione
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Keywords {🔍}
mitogcl, γglutamylcysteine, fig, article, cells, glutathione, mitochondrial, gsh, google, scholar, gcl, cas, neurons, supplementary, mitochondria, inactive, gpx, ros, nature, cell, mice, peroxidase, gss, expression, protein, form, fluorescence, data, neuronal, wildtype, panel, mutant, increase, min, injected, preinjected, analysis, cofactor, control, primary, antioxidant, human, activity, knockdown, expressed, hekt, almeida, bolaños, results, significant,
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nature portfolio n-methyl-d-aspartate receptor antagonist16 author information authors privacy policy n-methyl-d-aspartate receptors additional information advertising nature nitric oxide-mediated apoptosis social media middle panel γ-glutamylcysteine-mediated ros detoxification γ-glutamylcysteine-mediated o2·– detoxification designed research mitochondrial-targeted γ-glutamylcysteine biosynthesis 0/ reprints mitochondrial-targeting epitope-processed form performed research full-length cdna-encoding mitogcl author correspondence supplementary references reactive oxygen species 9-nucleotide stem-loop shrnas mouse development γ-glutamyltransferase forms γ-glutamylcysteine tat-mediated protein transduction article quintana-cabrera mitochondrial-targeted newly synthesized glutamyl-amino acid transporter2 high-pressure liquid chromatography high-performance liquid chromatography creative commons attribution-noncommercial supplementary tables s1-s3 targeting glutamate-cysteine ligase iron–sulfur cluster assembly gamma-glutamyl amino acids ice-cold orthophosphoric acid phyper-dmito plasmid vector nhei/xmai restriction enzymes newly synthesized γ-glutamylcysteine rabbit polyclonal anti-gcl received wild-type mitogcl consecutive atp-requiring steps pdf 441 kb γ-glutamylcysteine redox cycle protein thiol-redox modifications rabbit polyclonal anti-gfp impairing γ-glutamylcysteine biosynthesis mouse monoclonal anti-sod2 gene expression-specific knockdown
Questions {❓}
- Glutathione synthetase deficiency: is gamma-glutamylcysteine accumulation a way to cope with oxidative stress in cells with insufficient levels of glutathione?
- Oxidative stress in neurodegeneration: cause or consequence?
- Parkinson's disease: a disorder due to nigral glutathione deficiency?
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