Document Detail


Fructose-1,6-bisphosphate does not preserve ATP in hypoxic-ischemic neonatal cerebrocortical slices.
MedLine Citation:
PMID:  18725216     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fructose-1,6-bisphosphate (FBP), an endogenous intracellular metabolite in glycolysis, was found in many preclinical studies to be neuroprotective during hypoxia-ischemia (HI) when administered exogenously. We looked for HI neuroprotection from FBP in a neonatal rat brain slice model, using 14.1 T (1)H/(31)P/(13)C NMR spectroscopy of perchloric acid slice extracts to ask: 1) if FBP preserves high energy phosphates during HI; and 2) if exogenous [1-(13)C]FBP enters cells and is glycolytically metabolized to [3-(13)C]lactate. We also asked: 3) if substantial superoxide production occurs during and after HI, thinking such might be treatable by exogenous FBP's antioxidant effects. Superfused P7 rat cerebrocortical slices (350 mum) were treated with 2 mM FBP before and during 30 min of HI, and then given 4 h of recovery with an FBP-free oxygenated superfusate. Slices were removed before HI, at the end of HI, and at 1 and 4 h after HI. FBP did not improve high energy phosphate levels or change (1)H metabolite profiles. Large increases in [3-(13)C]lactate were seen with (13)C NMR, but the lactate fractional enrichment was always (1.1+/-0.5)%, implying that all of lactate's (13)C was natural abundance (13)C, that none was from metabolism of (13)C-FBP. FBP had no effect on the fluorescence of ethidium produced from superoxide oxidation of hydroethidine. Compared to control slices, ethidium fluorescence was 25% higher during HI and 50% higher at the end of recovery. Exogenous FBP did not provide protection or enter glycolysis. Its use as an antioxidant might be worth studying at higher FBP concentrations.
Authors:
Jia Liu; Kiyoshi Hirai; Lawrence Litt
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-12
Journal Detail:
Title:  Brain research     Volume:  1238     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-22     Completed Date:  2009-02-09     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  230-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism*
Animals
Animals, Newborn
Cerebral Cortex / drug effects*,  metabolism
Fructosediphosphates / metabolism,  pharmacology*
Hypoxia-Ischemia, Brain / metabolism,  prevention & control*
Neuroprotective Agents / metabolism,  pharmacology*
Organ Culture Techniques
Rats
Rats, Sprague-Dawley
Spectrum Analysis
Superoxides / metabolism
Grant Support
ID/Acronym/Agency:
R01 GM034767/GM/NIGMS NIH HHS; R01 GM034767-20/GM/NIGMS NIH HHS; R01 GM34767/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Fructosediphosphates; 0/Neuroprotective Agents; 11062-77-4/Superoxides; 8L70Q75FXE/Adenosine Triphosphate; M7522JYX1H/fructose-1,6-diphosphate
Comments/Corrections

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