title: Glutamate induces H2O2 synthesis in nonsynaptic brain mitochondria.
abstract: 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 50 μM 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 Ca(2+) (20 μM) 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 (10 μM) and D-AP5 (20 μM) 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.
authors.affiliation: Belozersky Research Institute for Physico Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; Research Institute of Cytochemistry and Molecular Pharmacology, ul. 6-ya Radialnaya 24, Building 14, 115404 Moscow, Russia. Electronic address: nlobysheva@gmail.com.
authors.forename: N V
authors.initials: NV
authors.lastname: Lobysheva
authors.affiliation: Research Institute of Cytochemistry and Molecular Pharmacology, ul. 6-ya Radialnaya 24, Building 14, 115404 Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Selin
authors.affiliation: Belozersky Research Institute for Physico Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
authors.forename: I M
authors.initials: IM
authors.lastname: Vangeli
authors.affiliation: Belozersky Research Institute for Physico Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
authors.forename: I M
authors.initials: IM
authors.lastname: Byvshev
authors.affiliation: Belozersky Research Institute for Physico Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
authors.forename: L S
authors.initials: LS
authors.lastname: Yaguzhinsky
authors.affiliation: Research Institute of Cytochemistry and Molecular Pharmacology, ul. 6-ya Radialnaya 24, Building 14, 115404 Moscow, Russia.
authors.forename: Y R
authors.initials: YR
authors.lastname: Nartsissov
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018698:Glutamic Acid; D006861:Hydrogen Peroxide
keywords: Glutamate; Hydrogen peroxide; Mitochondria; N-methyl-D-aspartate; NMDA; ROS; SDH; Succinate dehydrogenase; reactive oxygen species