Glutamate induces H₂O₂ synthesis in nonsynaptic brain mitochondria

Mitochondrial reactive oxygen species regulate many important biological processes. We studied H₂O₂ formation by nonsynaptic brain mitochondria in response to the addition of low concentrations of glutamate, an excitatory neurotransmitter. We demonstrated that glutamate at concentrations from 10 to...

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Published inFree radical biology & medicine Vol. 65; pp. 428 - 435
Main Authors Lobysheva, N.V, Selin, A.A, Vangeli, I.M, Byvshev, I.M, Yaguzhinsky, L.S, Nartsissov, Y.R
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.12.2013
Subjects
Animals
brain
Brain - metabolism
calcium
electron transport chain
glutamic acid
Glutamic Acid - metabolism
hydrogen peroxide
Hydrogen Peroxide - metabolism
Microscopy, Electron, Transmission
mitochondria
Mitochondria - metabolism
Rats
Rats, Wistar
Mitochondria
Succinate dehydrogenase
Hydrogen peroxide
SDH
ROS
reactive oxygen species
NMDA
N-methyl-D-aspartate
Glutamate
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Summary:Mitochondrial reactive oxygen species regulate many important biological processes. We studied H₂O₂ formation by nonsynaptic brain mitochondria in response to the addition of low concentrations of glutamate, an excitatory neurotransmitter. We demonstrated that glutamate at concentrations from 10 to 50μM stimulated the H₂O₂ generation in mitochondria up to 4-fold, in a dose-dependent manner. The effect of glutamate was observed only in the presence of Ca²⁺ (20μM) in the incubation medium, and the rate of calcium uptake by the brain mitochondria was increased by up to 50% by glutamate. Glutamate-dependent effects were sensitive to the NMDA receptor inhibitors MK-801 (10μM) and D-AP5 (20μM) and the inhibitory neurotransmitter glycine (5mM). We have shown that the H₂O₂ formation caused by glutamate is associated with complex II and is dependent on the mitochondrial potential. We have found that nonsynaptic brain mitochondria are a target of direct glutamate signaling, which can specifically activate H₂O₂ formation through mitochondrial respiratory chain complex II. The H₂O₂ formation induced by glutamate can be blocked by glycine, an inhibitory neurotransmitter that prevents the deleterious effects of glutamate in brain mitochondria.
Bibliography:http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.030
ObjectType-Article-1
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ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2013.07.030