Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit.

Détails

ID Serval
serval:BIB_89D1C678ED98
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit.
Périodique
Journal of Neurochemistry
Auteur⸱e⸱s
Lavoie S., Chen Y., Dalton T.P., Gysin R., Cuénod M., Steullet P., Do K.Q.
ISSN
1471-4159[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
108
Numéro
6
Pages
1410-1422
Langue
anglais
Résumé
A decrease in GSH levels, the main redox regulator, can be observed in neurodegenerative diseases as well as in schizophrenia. In search for substances able to increase GSH, we evaluated the ability of curcumin (polyphenol), quercetin (flavonoid), and tert-butylhydroquinone (tBHQ) to up-regulate GSH-synthesizing enzymes. The gene expression, activity, and product levels of these enzymes were measured in cultured neurons and astrocytes. In astrocytes, all substances increased GSH levels and the activity of the rate-limiting synthesizing enzyme, glutamate cysteine ligase (GCL). In neurons, curcumin and to a lesser extent tBHQ increased GCL activity and GSH levels, while quercetin decreased GSH and led to cell death. In the two cell types, the gene that showed the greatest increase in its expression was the one coding for the modifier subunit of GCL (GCLM). The increase in mRNA levels of GCLM was 3 to 7-fold higher than that of the catalytic subunit. In astrocytes from GCLM-knock-out mice showing low GSH (-80%) and low GCL activity (-50%), none of the substances succeeded in increasing GSH synthesis. Our results indicate that GCLM is essential for the up-regulation of GCL activity induced by curcumin, quercetin and tBHQ.
Mots-clé
Analysis of Variance, Animals, Antioxidants/pharmacology, Astrocytes/drug effects, Cell Survival/drug effects, Cells, Cultured, Cerebral Cortex/cytology, Curcumin/pharmacology, Dose-Response Relationship, Drug, Embryo, Mammalian, Enzyme Inhibitors/pharmacology, Gene Expression/drug effects, Glutamate-Cysteine Ligase/antagonists &amp, inhibitors, Glutamate-Cysteine Ligase/chemistry, Glutathione/metabolism, Hydroquinones/pharmacology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons/drug effects, Protein Subunits/deficiency, Protein Subunits/genetics, Quercetin/pharmacology, Up-Regulation/drug effects
Pubmed
Web of science
Création de la notice
16/03/2009 10:06
Dernière modification de la notice
20/08/2019 14:48
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