Nuclear factor erythroid 2-related factor 2 facilitates neuronal glutathione synthesis by upregulating neuronal excitatory amino acid transporter 3 expression.

Détails

ID Serval
serval:BIB_2BAA0711AB00
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Nuclear factor erythroid 2-related factor 2 facilitates neuronal glutathione synthesis by upregulating neuronal excitatory amino acid transporter 3 expression.
Périodique
Journal of Neuroscience
Auteur(s)
Escartin C., Won S.J., Malgorn C., Auregan G., Berman A.E., Chen P.C., Déglon N., Johnson J.A., Suh S.W., Swanson R.A.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
2011
Volume
31
Numéro
20
Pages
7392-7401
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.Publication Status: ppublish
Résumé
Astrocytes support neuronal antioxidant capacity by releasing glutathione, which is cleaved to cysteine in brain extracellular space. Free cysteine is then taken up by neurons through excitatory amino acid transporter 3 [EAAT3; also termed Slc1a1 (solute carrier family 1 member 1)] to support de novo glutathione synthesis. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway by oxidative stress promotes astrocyte release of glutathione, but it remains unknown how this release is coupled to neuronal glutathione synthesis. Here we evaluated transcriptional regulation of the neuronal cysteine transporter EAAT3 by the Nrf2-ARE pathway. Nrf2 activators and Nrf2 overexpression both produced EAAT3 transcriptional activation in C6 cells. A conserved ARE-related sequence was found in the EAAT3 promoter of several mammalian species. This ARE-related sequence was bound by Nrf2 in mouse neurons in vivo as observed by chromatin immunoprecipitation. Chemical activation of the Nrf2-ARE pathway in mouse brain increased both neuronal EAAT3 levels and neuronal glutathione content, and these effects were abrogated in mice genetically deficient in either Nrf2 or EAAT3. Selective overexpression of Nrf2 in brain neurons by lentiviral gene transfer was sufficient to upregulate both neuronal EAAT3 protein and glutathione content. These findings identify a mechanism whereby Nrf2 activation can coordinate astrocyte glutathione release with neuronal glutathione synthesis through transcriptional upregulation of neuronal EAAT3 expression.
Mots-clé
Animals, Cell Line, Tumor, Excitatory Amino Acid Transporter 3/biosynthesis, Excitatory Amino Acid Transporter 3/deficiency, Glutathione/biosynthesis, Male, Marmota, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-E2-Related Factor 2/deficiency, NF-E2-Related Factor 2/genetics, Neurons/metabolism, Rats, Up-Regulation/genetics, Up-Regulation/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/12/2011 17:12
Dernière modification de la notice
08/05/2019 16:21
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