| Pyruvate protects neurons against hydrogen peroxide-induced toxicity. | |
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MedLine Citation:
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PMID: 9364052 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hydrogen peroxide (H2O2) is suspected to be involved in numerous brain pathologies such as neurodegenerative diseases or in acute injury such as ischemia or trauma. In this study, we examined the ability of pyruvate to improve the survival of cultured striatal neurons exposed for 30 min to H2O2, as estimated 24 hr later by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay. Pyruvate strongly protected neurons against both H2O2 added to the external medium and H2O2 endogenously produced through the redox cycling of the experimental quinone menadione. The neuroprotective effect of pyruvate appeared to result rather from the ability of alpha-ketoacids to undergo nonenzymatic decarboxylation in the presence of H2O2 than from an improvement of energy metabolism. Indeed, several other alpha-ketoacids, including alpha-ketobutyrate, which is not an energy substrate, reproduced the neuroprotective effect of pyruvate. In contrast, lactate, a neuronal energy substrate, did not protect neurons from H2O2. Optimal neuroprotection was achieved with relatively low concentrations of pyruvate (</=1 mM), whereas at high concentration (10 mM) pyruvate was ineffective. This paradox could result from the cytosolic acidification induced by the cotransport of pyruvate and protons into neurons. Indeed, cytosolic acidification both enhanced the H2O2-induced neurotoxicity and decreased the rate of pyruvate decarboxylation by H2O2. Together, these results indicate that pyruvate efficiently protects neurons against both exogenous and endogenous H2O2. Its low toxicity and its capacity to cross the blood-brain barrier open a new therapeutic perspective in brain pathologies in which H2O2 is involved. |
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Authors:
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S Desagher; J Glowinski; J Prémont |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 17 ISSN: 0270-6474 ISO Abbreviation: J. Neurosci. Publication Date: 1997 Dec |
Date Detail:
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Created Date: 1997-12-15 Completed Date: 1997-12-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9060-7 Citation Subset: IM |
Affiliation:
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Chaire de Neuropharmacologie, Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75 231 Paris Cedex 05, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Butyric Acids / pharmacology Cells, Cultured Corpus Striatum / cytology* Energy Metabolism / drug effects Hydrogen Peroxide / toxicity* Hydrogen-Ion Concentration Ketoglutaric Acids / pharmacology Lactic Acid / pharmacology Mice Neurons / drug effects* Neuroprotective Agents / pharmacology* Oxaloacetates / pharmacology Oxaloacetic Acids Oxidation-Reduction Oxidative Stress / drug effects Pyruvic Acid / pharmacology* Vitamin K / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Butyric Acids; 0/Ketoglutaric Acids; 0/Neuroprotective Agents; 0/Oxaloacetates; 0/Oxaloacetic Acids; 12001-79-5/Vitamin K; 127-17-3/Pyruvic Acid; 328-50-7/alpha-ketoglutaric acid; 50-21-5/Lactic Acid; 600-18-0/alpha-ketobutyric acid; 7722-84-1/Hydrogen Peroxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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