Peroxynitrite inhibits glutamate transporter subtypes

Détails

ID Serval
serval:BIB_CAA93C65A72C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxynitrite inhibits glutamate transporter subtypes
Périodique
Journal of Biological Chemistry
Auteur(s)
Trotti  D., Rossi  D., Gjesdal  O., Levy  L. M., Racagni  G., Danbolt  N. C., Volterra  A.
ISSN
0021-9258 (Print)
Statut éditorial
Publié
Date de publication
03/1996
Volume
271
Numéro
11
Pages
5976-9
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Résumé
The reuptake of glutamate in neurons and astrocytes terminates excitatory signals and prevents the persistence of excitotoxic levels of glutamate in the synaptic cleft. This process is inhibited by oxygen radicals and hydrogen peroxide (H2O2). Here we show that another biological oxidant, peroxynitrite (ONOO-), formed by combination of superoxide (O2-) and nitric oxide (NO), potently inhibits glutamate uptake by purified or recombinant high affinity glutamate transporters reconstituted in liposomes. ONOO- reduces selectively the Vmax of transport; its action is fast (reaching > or = 90% within 20 s), dose-dependent (50% inhibition at 50 microM), persistent upon ONOO- (or by product) removal, and insensitive to the presence of the lipid antioxidant vitamin E in the liposomal membranes. Therefore, it likely depends on direct interaction of ONOO- with the glutamate transporters. Three distinct recombinant glutamate transporters from the rat brain, GLT1, GLAST, and EAAC1, exhibit identical sensitivity to ONOO . H2O2 also inhibits reconstituted transport, and its action matches that of ONOO- on all respects; however, this is observed only with 5-10 mM H202 and after prolonged exposure (10 min) in highly oxygenated buffer. NO, released from NO donors (up to 10 mM), does not modify reconstituted glutamate uptake, although in parallel conditions it promotes cGMP formation in synaptosomal cytosolic fraction. Overall, our results suggest that the glutamate transporters contain conserved sites in their structures conferring vulnerability to ONOO- and other oxidants.
Mots-clé
ATP-Binding Cassette Transporters/classification/genetics/*toxicity Amino Acid Transport System X-AG Animals Biological Transport, Active/drug effects Brain/metabolism Glutamic Acid/*metabolism Hela Cells Humans Kinetics Liposomes Nitrates/*toxicity Oxidants/toxicity Rats Recombinant Proteins/antagonists & inhibitors/genetics/metabolism Transfection
Pubmed
Web of science
Création de la notice
24/01/2008 15:37
Dernière modification de la notice
03/03/2018 21:25
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