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Glutamate as a regulator of ROS production by brain mitochondria under hypoxia/reoxygenation conditionsтезисы доклада
Информация о цитировании статьи получена из
Web of Science
Дата последнего поиска статьи во внешних источниках: 19 сентября 2015 г.
- Авторы: Lobysheva N.V., Selin A.A., Yaguzhinsky L.S., Nartsissov Y.R.
- Сборник: Biochim. Biophys. Acta - Bioenergetics, EBEC Short Reports
- Серия: Supplement
- Том: 1817
- Тезисы
- Год издания: 2012
- Издательство: ELSEVIER SCIENCE BV
- Местоположение издательства: PO BOX 211, AMSTERDAM, NETHERLANDS, 1000 AE
- Первая страница: 79
- DOI: 10.1016
- Аннотация: Hypoxia leads to a massive release of neurotransmitter glutamate resulting in overactivation of glutamate receptors during ischemic stroke. These processes are usually accompanied by elevation of hydrogen peroxide and nitric oxide generation which causes mitochondrial permeability transition and suppresses oxidative phosphorylation. Meanwhile, it is possible to assume that a direct signaling pathway linked hypoxia and mitochondria. Our aim was to study the main biochemical mechanisms realized in mitochondria during oxidation stress under hypoxia/reoxygenation conditions. We used a model of mitochondria isolated from rat brain using Percoll density centrifugation surviving under hypoxia. After 10 min of incubation under hypoxic conditions mitochondrial respiratory control index (RCI) was reduced by 40%. This reduction of RCI was accompanied by increased H2O2 generation. It was found that if the incubation of mitochondria was carried out in the presence of glycine 5 mM and MK-801 10 μM (an inhibitor of glutamate receptors), reduction of RCI and increase of H2O2 generation was significantly lower. Whereas hypoxia causes elevation of glutamate concentration we made a pioneering hypothesis that glutamate could activate signaling processes in mitochondria by itself. Indeed a very low dose of glutamate (5–50 μM) added to isolated mitochondria in the presence of rotenone (inhibitor of complex I mitochondrial respiratory chain) stimulates the generation of H2O2 up to 4 fold in a dose-dependent manner. The process was significantly reduced by MK-801 10 μM and glycine 5 mM. These results suggest the possible existence of a glutamate receptor in brain mitochondria. Our findings suggest a novel mechanism by which brain mitochondria could directly sense the signal of an elevated glutamate level under hypoxia.
- Добавил в систему: Ягужинский Лев Сергеевич