Dysregulation of Glutathione Metabolism: A Risk Factor for Schizophrenia

Détails

ID Serval
serval:BIB_AA401DC6AE7A
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
Dysregulation of Glutathione Metabolism: A Risk Factor for Schizophrenia
Auteur(s)
Gysin René, Tosic Curnier Mirjana, Chappuis Céline, Deppen Patricia, Ruiz Viviane, Cuénod Michel, Do Kim Quang
ISBN
0302-282X
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
54
Série
Neuropsychobiology
Pages
6
Langue
anglais
Notes
SAPHIRID:61718
Résumé
Schizophrenia is a complex multi-factorial psychiatric brain disorder. It affects individuals at the centre of their personality and concerns about 1% of the world population. Both environmental and genetic factors are implicated in the vulnerability to develthis disease. Previous studies showed reduced levels of glutathione (GSH), the main non protein cellular redox regulator, both in cerebrospinal fluid and prefrontal cortex of schizophrenia patients (Do et al. 2000). In case-control association studies for candidate genes of GSH metabolism we found a strong association between schizophrenia and single nucleotide polymorphisms in the GSH key synthesizing enzyme glutamate- cysteine-ligase (GCL) modifier subunit (GCLM) gene (Tosic et al. submitted). In this study we investigated if these genetic anomalies led to functional consequences at the protein expression, as well as at the enzyme activity levels. Since GSH is ubiquitously present in cells, these parameters of the GCL regulation were determined in fibroblasts derived from skin biopsies. Moreover, in the GCLM knock-out mouse model it was observed that the luck of GCLM led to an increased sensitivity to oxidative stress (Yang et al. 2002). We thus compared between patients and controls the functional parameters at baseline, as well as under oxidative stress induced conditions by treating cells with tert-buthylhydroquinone, a substance known to produce reactive oxygen species. In the presented study we observed that compared to controls schizophrenia patients had a reduced GCL activity under oxidative stress conditions, a reduced protein expression of GCLC under baseline, as well as under oxidative stress conditions, and an uncoupling of GCLM and GCLC protein expression in response to oxidative stress. Finally, in the group of patients we observed an inverse correlation between the levels of GSH increase under oxidative stress conditions and the severity of positive symptoms of the disease.
Open Access
Oui
Création de la notice
10/03/2008 10:49
Dernière modification de la notice
20/08/2019 15:14
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