Pyruvate dehydrogenase activity in the rat cerebral cortex following cerebral ischemia.
The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common carotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate was determined. In cortex from control animals, the rate of [1(-14)C]pyruvate decarboxylation was 9.6 +/- 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recovery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p. four times over 2 h, significantly decreased blood glucose levels from 7.4 +/- 0.6 to 5.1 +/- 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 +/- 0.5 mumol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 +/- 4%. In contrast, the depressed PDHC activity at 15 min following ischemia was not affected by the DCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardell
M
M
Laboratory of Experimental Brain Research, University of Lund, Lund Hospital, Sweden.
Koide
T
T
Wieloch
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002339:Carotid Arteries; D002540:Cerebral Cortex / Q000201:enzymology*; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004734:Energy Metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006019:Glycolysis; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose