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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
1998-7-7
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pubmed:abstractText |
The role of mitochondrial energy metabolism in glutamate mediated neurotoxicity was studied in rat neurones in primary culture. A brief (15 min) exposure of the neurones to glutamate caused a dose-dependent (0.01-1 mM) increase in cyclic GMP levels together with delayed (24 h) neurotoxicity and ATP depletion. These effects were prevented by either the nitric oxide (.NO) synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (NAME; 1 mM) or by the N-methyl-D-aspartate (NMDA) glutamate-subtype receptor antagonist D-(-)-2-amino-5-phosphonopentanoate (APV; 0.1 mM). Glutamate exposure (0.1 mM and 1 mM) followed by 24 h of incubation caused the inhibition of succinate-cytochrome c reductase (20-25%) and cytochrome c oxidase (31%) activities in the surviving neurones, without affecting NADH-coenzyme-Q1 reductase activity. The rate of oxygen consumption was impaired in neurones exposed to 1 mM glutamate, either with glucose (by 26%) or succinate (by 39%) as substrates. These effects on the mitochondrial respiratory chain and neuronal respiration, together with the observed glutathione depletion (20%) by glutamate exposure were completely prevented by NAME or APV. Our results suggest that mitochondrial dysfunction and impairment of antioxidant status may account for glutamate-mediated neurotoxicity via a mechanism involving .NO biosynthesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-Amino-5-phosphonovalerate,
http://linkedlifedata.com/resource/pubmed/chemical/Antimycin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Nos1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Protective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Rotenone,
http://linkedlifedata.com/resource/pubmed/chemical/Succinic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Uncoupling Agents,
http://linkedlifedata.com/resource/pubmed/chemical/antimycin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-8993
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 1998 Elsevier Science B.V.
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
790
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
209-16
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:9593899-2-Amino-5-phosphonovalerate,
pubmed-meshheading:9593899-Animals,
pubmed-meshheading:9593899-Antimycin A,
pubmed-meshheading:9593899-Cell Respiration,
pubmed-meshheading:9593899-Cells, Cultured,
pubmed-meshheading:9593899-Cerebral Cortex,
pubmed-meshheading:9593899-Cyclic GMP,
pubmed-meshheading:9593899-Enzyme Inhibitors,
pubmed-meshheading:9593899-Excitatory Amino Acid Antagonists,
pubmed-meshheading:9593899-Glucose,
pubmed-meshheading:9593899-Glutamic Acid,
pubmed-meshheading:9593899-Glutathione,
pubmed-meshheading:9593899-Mitochondria,
pubmed-meshheading:9593899-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:9593899-Nerve Degeneration,
pubmed-meshheading:9593899-Nerve Tissue Proteins,
pubmed-meshheading:9593899-Neurons,
pubmed-meshheading:9593899-Neurotoxins,
pubmed-meshheading:9593899-Nitric Oxide Synthase,
pubmed-meshheading:9593899-Nitric Oxide Synthase Type I,
pubmed-meshheading:9593899-Radiation-Protective Agents,
pubmed-meshheading:9593899-Rats,
pubmed-meshheading:9593899-Rats, Wistar,
pubmed-meshheading:9593899-Rotenone,
pubmed-meshheading:9593899-Succinic Acid,
pubmed-meshheading:9593899-Uncoupling Agents
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pubmed:year |
1998
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pubmed:articleTitle |
Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial dysfunction and glutathione depletion.
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pubmed:affiliation |
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Salamanca, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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