Aug 30, 2008

Fructose-1,6-bisphosphate does not preserve ATP in hypoxic-ischemic neonatal cerebrocortical slices

Brain Research
Jia LiuLawrence Litt


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 metaboli...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Ethyl pyruvate
Biochemical Pathway
Calcium [EPC]
Dimethyl Sulfoxide
Organ Culture Techniques

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