Fructose-1,6-bisphosphate stabilizes brain intracellular calcium during hypoxia in rats.
OBJECTIVE
Exogenously administered fructose-1,6-bisphosphate reduces neuronal injury from hypoxic or ischemic brain insults. To test the hypothesis that fructose-1,6-bisphosphate prevents changes in intracellular calcium ([Ca2+]i) and high-energy phosphate levels, we measured [Ca2+]i, intracellular pH (pHi), and adenosine triphosphate in cultured rat cortical astrocytes and cortical brain slices during hypoxia.


METHODS
The fluorescent indicators fura-2 and bis-carboxyethyl-carboxyfluorescein were used to simultaneously measure [Ca2+]i and pHi with a fluorometer.


RESULTS
Exposure to hypoxia (95% N2, 5% CO2) or 100 microM sodium cyanide produced transient increases in [Ca2+]i in astrocytes and sustained increases in [Ca2+]i in brain slices. Adenosine triphosphate levels fell in slices exposed to hypoxia or cyanide. Fructose-1,6-bisphosphate (3.5 mM) blocked increases in [Ca2+]i and prevented depletion of adenosine triphosphate. Fructose-1,6-bisphosphate also partially prevented adenosine triphosphate depletion in brain slices incubated in glucose-free medium. Iodoacetate (a specific inhibitor of glycolysis) elevated [Ca2+]i and partially prevented these actions of fructose-1,6-bisphosphate. Changes in pHi during hypoxia were not affected by fructose-1,6-bisphosphate.


CONCLUSIONS
Fructose-1,6-bisphosphate supports adenosine triphosphate production via stimulation of glycolysis and results in the maintenance of normal [Ca2+]i during hypoxia or hypoglycemia.
Bickler
P E
PE
Department of Anesthesia, University of California, San Francisco 94143-0542.
Kelleher
J A
JA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005635:Fructosediphosphates / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley
D005635:Fructosediphosphates; D007461:Iodoacetates; D000255:Adenosine Triphosphate; C029063:fructose-1,6-diphosphate; D002118:Calcium; D019807:Iodoacetic Acid