Document Detail


Pyruvate protects neurons against hydrogen peroxide-induced toxicity.
MedLine Citation:
PMID:  9364052     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S Desagher; J Glowinski; J Prémont
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  1997-12-15     Completed Date:  1997-12-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9060-7     Citation Subset:  IM    
Affiliation:
Chaire de Neuropharmacologie, Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75 231 Paris Cedex 05, France.
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MeSH Terms
Descriptor/Qualifier:
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:
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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