Document Detail


Protection of astrocytes by fructose 1,6-bisphosphate and citrate ameliorates neuronal injury under hypoxic conditions.
MedLine Citation:
PMID:  8836557     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fructose 1,6-bisphosphate (FBP) protects astrocytes from hypoxic injury in vitro. To determine whether FBP and citrate (inhibitors of phosphofructokinase) ameliorate hypoxia-induced injury to neurons and, if they do, whether the protective effects are a direct result of their actions on neurons or a consequence of their actions on astrocytes, we added FBP or citrate to the media of normoxic and hypoxic 'pure', mixed and co-culture systems. FBP (3.5 mM) and citrate (10 microM-2 mM) decreased release of LDH from astrocytes following 24 h of hypoxia. Eight hours of hypoxia killed pure neuronal cultures and neither FBP nor citrate prevented this death. However, in mixed and co-culture systems, FBP and citrate increased neuronal viability (as determined by the ratio of live-to-total cells), even after 47 h of hypoxia. In co-culture, following 24 h of hypoxia, both FBP and citrate reduced neuronal release of LDH and neuronal death. Fluorocitrate, a suicidal-inhibitor of aconitase, also protected astrocytes, but not neurons, from hypoxia in 'pure' culture, presumably by increasing intracellular citrate concentrations through inhibition of the catalysis of citrate to isocitrate We conclude that FBP and citrate attenuate hypoxic neuronal injury through their effects on astrocytes.
Authors:
J A Kelleher; T Y Chan; P H Chan; G A Gregory
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  726     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1997-02-13     Completed Date:  1997-02-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  167-73     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, University of California School of Medicine, San Francisco 94143, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / drug effects*,  enzymology
Cell Survival / drug effects
Cells, Cultured
Citric Acid / pharmacology*
Enzyme Inhibitors / pharmacology*
Fructokinases / antagonists & inhibitors*
Fructosediphosphates / pharmacology*
Hypoxia, Brain / drug therapy*,  pathology
L-Lactate Dehydrogenase / metabolism
Neurons / drug effects*,  enzymology,  pathology
Neuroprotective Agents / pharmacology*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
NS-14543/NS/NINDS NIH HHS; NS-20692/NS/NINDS NIH HHS; NS-25372/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fructosediphosphates; 0/Neuroprotective Agents; 488-69-7/fructose-1,6-diphosphate; 77-92-9/Citric Acid; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.1.-/Fructokinases; EC 2.7.1.4/fructokinase

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


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