Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia.

@article{Gysin2011GeneticDO,
  title={Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia.},
  author={Ren{\'e} Gysin and Rudolf Kraftsik and Olivier Boulat and Pierre Bovet and Philippe Conus and Emily Comte-Krieger and Andrea Polari and Pascal Steullet and Martin Preisig and Tanja Teichmann and Michel Cu{\'e}nod and Kim Q. Do},
  journal={Antioxidants \& redox signaling},
  year={2011},
  volume={15 7},
  pages={
          2003-10
        }
}
Genetic studies have shown an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL), the key enzyme for glutathione (GSH) synthesis. The present study was aimed at analyzing the influence of a GSH dysregulation of genetic origin on plasma thiols (total cysteine, homocysteine, and cysteine-glycine) and other free amino acid levels as well as fibroblast cultures GSH levels. Plasma thiols levels… 
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Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis.
TLDR
GCLC high-risk genotypes are associated with low [GSHmPFC], highlighting that GCLC polymorphisms should be considered in pathology studies of cerebral GSH.
Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with schizophrenia: A case-control study in a Tunisian population
Implication of the glutamate–cystine antiporter xCT in schizophrenia cases linked to impaired GSH synthesis
TLDR
The results support the implication of xCT dysregulation in illness pathophysiology and indicate that it can result from redox changes and add to the existing evidence identifying the inflammatory/redox systems as important targets to treat schizophrenia already at early stages.
Glutathione levels and activities of glutathione metabolism enzymes in patients with schizophrenia: A systematic review and meta-analysis
TLDR
There may be glutathione deficits and abnormalities in the glutATHione redox cycle in patients with schizophrenia, however, given the small number of studies examined the entire glutathion system, further studies are needed to elucidate a better understanding of disrupted glutathION function in schizophrenia.
Increased serum levels of cysteine in patients with schizophrenia: A potential marker of cognitive function preservation
Alterations in the Antioxidant Enzyme Activities in the Neurodevelopmental Rat Model of Schizophrenia Induced by Glutathione Deficiency during Early Postnatal Life
TLDR
This analysis showed that treatment with a BSO + GBR 12909 combination caused significant decreases in the lipid peroxidation levels in the PFC and HIP, in spite of there being no changes in ROS.
Glutathione Deficiency and Alterations in the Sulfur Amino Acid Homeostasis during Early Postnatal Development as Potential Triggering Factors for Schizophrenia-Like Behavior in Adult Rats
TLDR
The results suggest the usefulness of this neurodevelopmental model for research on the pathomechanism of schizophrenia and the effects of l-buthionine-(S,R)-sulfoximine (BSO) and GBR 12909 on the levels of GSH, sulfur amino acids, global DNA methylation, and schizophrenia-like behavior in Sprague–Dawley rats in adulthood.
Impaired metabolic reactivity to oxidative stress in early psychosis patients.
TLDR
Results indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis, and protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.
Effects of antipsychotics on antioxidant defence system in patients with schizophrenia: A meta-analysis
[Glutathione reductase and glutathione-S-transferase in blood cells in schizophrenia and schizophrenia spectrum disorders].
TLDR
The correlations linking the basal levels of GR and GST activities with the results of clinical assessments after treatment allow us to consider these parameters as potential biomarkers for predicting treatment response.
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References

SHOWING 1-10 OF 74 REFERENCES
Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence
TLDR
Genetic and functional evidence is provided that an impaired capacity to synthesize GSH under conditions of oxidative stress is a vulnerability factor for schizophrenia.
Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction.
Altered Glutathione Redox State in Schizophrenia
TLDR
Levels of GSH, GSSG, GPx, GSH and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects and positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions.
2.5 Redox Dysregulation in Schizophrenia: Genetic Susceptibility and Pathophysiological Mechanisms
TLDR
It is proposed that a brain glutathione deficit leads to the depression of N-methyl-D-aspartate responses and affect synaptic contacts in catecholamine innervated regions, as well as memory and sensory integration impairments similar to that observed in schizophrenia.
Polymorphism in the 5'-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction.
TLDR
Findings suggest that the -588T polymorphism of the GCLM gene may suppress G CLM gene induction in response to oxidants and that it is a genetic risk factor for MI.
Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene.
TLDR
Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder, and the gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia.
Oxidative/Nitrative Modifications of Plasma Proteins and Thiols from Patients with Schizophrenia
TLDR
It is suggested that the amount of carbonyl groups and 3-nitrotyrosine in plasma proteins may be important indicators of protein damage in vivo in schizophrenia.
Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients
Effect of thiol oxidation and thiol export from erythrocytes on determination of redox status of homocysteine and other thiols in plasma from healthy subjects and patients with cerebral infarction.
Changes in concentration of reduced and oxidized low-M(r) thiols were measured in blood and plasma before and after the separation of blood cells. If centrifugation of blood was postponed, the…
Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels.
  • L. Bekris, C. Shephard, +8 authors Å. Lernmark
  • Biology, Medicine
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
  • 2007
TLDR
T1D patients with an age-at-onset of 14-35 years who possess the GCLC -129 SNP T/T genotype have a higher GAD65Ab index than T1D Patients with the GclC - 129 SNP C/C genotype, and results suggest that G CLC promoter polymorphisms may influence G AD65Ab levels and may influence the age at which T1d is diagnosed.
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