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

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State: Public
Version: author
Serval ID
serval:BIB_43FDB52BB2BB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia.
Journal
Antioxidants and Redox Signaling
Author(s)
Gysin R., Kraftsik R., Boulat O., Bovet P., Conus P., Comte-Krieger E., Polari A., Steullet P., Preisig M., Teichmann T., Cuénod M., Do K.Q.
ISSN
1557-7716 (Electronic)
ISSN-L
1523-0864
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
15
Number
7
Pages
2003-2010
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Abstract 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 were also compared between patients and controls. As compared with patients with a low-risk GCLC GAG TNR genotype, patients with a high-risk genotype, having an impaired GSH synthesis, displayed a decrease of fibroblast GSH and plasma total cysteine levels, and an increase of the oxidized form of cysteine (cystine) content. Increased levels of plasma free serine, glutamine, citrulline, and arginine were also observed in the high-risk genotype. Taken together, the high-risk genotypes were associated with a subgroup of schizophrenia characterized by altered plasma thiols and free amino acid levels that reflect a dysregulation of redox control and an increased susceptibility to oxidative stress. This altered pattern potentially contributes to the development of a biomarker profile useful for early diagnosis and monitoring the effectiveness of novel drugs targeting redox dysregulation in schizophrenia. Antioxid. Redox Signal. 15, 2003-2010.
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Web of science
Create date
14/03/2011 10:21
Last modification date
20/08/2019 14:48
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