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Cited by 372

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Peroxynitrite Inhibits Glutamate Transporter Subtypes

Open access
Trotti, Davide, Rossi, Daniela, Gjesdal, Ola, Levy, Line M., Racagni, Giorgio, Danbolt, Niels C., Volterra, Andrea·1996·Journal of Biological Chemistry
DOI 10.1074/jbc.271.11.5976
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Abstract

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.

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Metadata

Authors
Trotti, D., Rossi, D., Gjesdal, O., Levy, L. M., Racagni, G., Danbolt, N. C., & Volterra, A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1996-03
Volume
271
Issue
11
Pages
5976-5979
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.271.11.5976
OpenAlex
W2058382351
Cited by
372
References
2
FWCI
9.28
Type
journal article
Language
en
Open access
hybrid

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