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Effect of Peroxynitrite on the Mitochondrial Respiratory Chain: Differential Susceptibility of Neurones and Astrocytes in Primary Culture
Author(s) -
Bolaños Juan P.,
Heales Simon J. R.,
Land John M.,
Clark John B.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64051965.x
Subject(s) - peroxynitrite , mitochondrial respiratory chain , glutathione , mitochondrion , biochemistry , respiratory chain , nitric oxide , cytochrome c oxidase , lactate dehydrogenase , cytochrome c , succinate dehydrogenase , glutathione reductase , chemistry , neurotoxicity , nitric oxide synthase , biology , superoxide , glutathione peroxidase , enzyme , toxicity , endocrinology , organic chemistry
The effect of the neurotoxic nitric oxide derivative, the peroxynitrite anion (ONOO − ), on the activity of the mitochondrial respiratory chain complexes in cultured neurones and astrocytes was studied. A single exposure of the neurones to ONOO − (initial concentrations of 0.01–2.0 m M ) caused, after a subsequent 24‐h incubation, a dose‐dependent decrease in succinate‐cytochrome c reductase (60% at 0.5 m M ) and in cytochrome c oxidase (52% at 0.5 m M ) activities. NADH‐ubiquinone‐1 reductase was unaffected. In astrocytes, the activity of the mitochondrial complexes was not affected up to 2 m M ONOO − . Citrate synthase was unaffected in both cell types under all conditions studied. However, lactate dehydrogenase activity released to the culture medium was increased by ONOO − in a dose‐dependent manner (40% at 0.5 m M ONOO − ) from the neurones but not from the astrocytes. Neuronal glutathione concentration decreased by 39% at 0.1 m M ONOO − , but astrocytic glutathione was not affected up to 2 m M ONOO − . In isolated brain mitochondria, only succinate‐cytochrome c reductase activity was affected (22% decrease at 1 m M ONOO − ). We conclude that the acute exposure of ONOO − selectively damages neurones, whereas astrocytes remain unaffected. Intracellular glutathione appears to be an important factor for ameliorating ONOO − ‐mediated mitochondrial damage. This study supports the hypothesis that the neurotoxicity of nitric oxide is mediated through mitochondrial dysfunction.