Document Detail


Inhibition of mitochondrial function in astrocytes: implications for neuroprotection.
MedLine Citation:
PMID:  17488276     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Much evidence suggests that astrocytes protect neurons against ischemic injury. Although astrocytes are more resistant to some insults than neurons, few studies offer insight into the real time changes of astrocytic protective functions with stress. Mitochondria are one of the primary targets of ischemic injury in astrocytes. We investigated the time course of changes in astrocytic ATP levels, plasma membrane potential, and glutamate uptake, a key protective function, induced by mitochondrial inhibition. Our results show that significant functional change precedes reduction in astrocytic viability with mitochondrial inhibition. Using the mitochondrial inhibitor fluorocitrate (FC, 0.25 mmol/L) that is preferentially taken by astrocytes we found that inhibition of astrocyte mitochondria increased vulnerability of co-cultured neurons to glutamate toxicity. In our studies, the rates of FC-induced astrocytic mitochondrial depolarization were accelerated in mixed astrocyte/neuron cultures. We hypothesized that the more rapid mitochondrial depolarization was promoted by an additional energetic demand imposed be the co-cultured neurons. To test this hypothesis, we exposed pure astrocytic cultures to 0.01-1 mmol/L aspartate as a metabolic load. Aspartate application accelerated the rates of FC-induced mitochondrial depolarization, and, at 1 mmol/L, induced astrocytic death, suggesting that strong energetic demands during ischemia can compromise astrocytic function and viability.
Authors:
Ludmila A Voloboueva; Sang Won Suh; Raymond A Swanson; Rona G Giffard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  102     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-30     Completed Date:  2007-10-04     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1383-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Animals, Newborn
Astrocytes / drug effects,  ultrastructure*
Cell Death / drug effects,  physiology
Cells, Cultured
Cerebral Cortex / cytology
Citrates / pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Glutamic Acid / pharmacology
Membrane Potential, Mitochondrial / drug effects,  physiology
Membrane Potentials / drug effects,  physiology
Mice
Mitochondria / drug effects*,  physiology
Neurons / drug effects,  physiology*
Neuroprotective Agents / pharmacology*
Time Factors
Grant Support
ID/Acronym/Agency:
GM49831/GM/NIGMS NIH HHS; NS014543/NS/NINDS NIH HHS; NS053898/NS/NINDS NIH HHS; NS37520/NS/NINDS NIH HHS; R01 GM049831/GM/NIGMS NIH HHS; R01 GM049831-15/GM/NIGMS NIH HHS; R01 NS053898/NS/NINDS NIH HHS; R01 NS053898-01A2/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Citrates; 0/Neuroprotective Agents; 357-89-1/fluorocitrate; 3KX376GY7L/Glutamic Acid; 8L70Q75FXE/Adenosine Triphosphate
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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