Skin fibroblast model to study an impaired glutathione synthesis: consequences of a genetic polymorphism on the proteome.

Détails

ID Serval
serval:BIB_7BAA49DEE938
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Skin fibroblast model to study an impaired glutathione synthesis: consequences of a genetic polymorphism on the proteome.
Périodique
Brain research bulletin
Auteur(s)
Gysin R., Riederer I.M., Cuénod M., Do K.Q., Riederer B.M.
ISSN
1873-2747 (Electronic)
ISSN-L
0361-9230
Statut éditorial
Publié
Date de publication
06/04/2009
Peer-reviewed
Oui
Volume
79
Numéro
1
Pages
46-52
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
An impaired glutathione (GSH) synthesis was observed in several multifactorial diseases, including schizophrenia and myocardial infarction. Genetic studies revealed an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL). Disease-associated genotypes of this polymorphism correlated with a decrease in GCLC protein expression, GCL activity and GSH content. To clarify consequences of a decreased GCL activity at the proteome level, three schizophrenia patients and three controls have been selected based on the GCLC GAG TNR polymorphism. Fibroblast cultures were obtained by skin biopsy and were challenged with tert-butylhydroquinone (t-BHQ), a substance known to induce oxidative stress. Proteome changes were analyzed by two dimensional gel electrophoresis (2-DE) and results revealed 10 spots that were upregulated in patients following t-BHQ treatment, but not in controls. Nine corresponding proteins could be identified by MALDI mass spectrometry and these proteins are involved in various cellular functions, including energy metabolism, oxidative stress response, and cytoskeletal reorganization. In conclusion, skin fibroblasts of subjects with an impaired GSH synthesis showed an altered proteome reaction in response to oxidative stress. Furthermore, the study corroborates the use of fibroblasts as an additional mean to study vulnerability factors of psychiatric diseases.

Mots-clé
Adult, Antioxidants/administration & dosage, Biopsy, Blotting, Western, Cells, Cultured, Electrophoresis, Gel, Two-Dimensional, Female, Fibroblasts/metabolism, Glutamate-Cysteine Ligase/genetics, Glutamate-Cysteine Ligase/metabolism, Glutathione/biosynthesis, Humans, Hydroquinones/administration & dosage, Male, Oxidative Stress, Polymorphism, Genetic, Proteome/metabolism, Schizophrenia/genetics, Schizophrenia/metabolism, Sequence Analysis, DNA, Skin, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Trinucleotide Repeats
Pubmed
Web of science
Création de la notice
06/02/2009 11:57
Dernière modification de la notice
03/03/2018 18:36
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