Hepatic preconditioning preserves energy metabolism during sustained ischemia.
We evaluated the possibility that ischemic preconditioning could modify hepatic energy metabolism during ischemia. Accordingly, high-energy nucleotides and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonpreconditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflecting slower adenine nucleotide degradation. These effects were associated with a decrease in glycogen depletion and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, reducing the availability of fructose-2, 6-bisphosphate. Preconditioning sustained metabolite concentration at higher levels although this was not correlated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. Our results suggest the induction of metabolic arrest and/or associated metabolic downregulation as energetic cost-saving mechanisms that could be induced by preconditioning.
Peralta
C
C
Unitat de Bioquímica, Campus de Bellvitge, Universitat de Barcelona, Spain.
Bartrons
R
R
Riera
L
L
Manzano
A
A
Xaus
C
C
Gelpí
E
E
Roselló-Catafau
J
J
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005635:Fructosediphosphates / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D007511:Ischemia / Q000378:metabolism*; D019194:Ischemic Preconditioning; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000201:enzymology*; D008297:Male; D025481:Phosphofructokinase-2; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats
D005635:Fructosediphosphates; D005636:Fructosephosphates; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D019298:Glucose-6-Phosphate; D000244:Adenosine Diphosphate; C027618:fructose-6-phosphate; C027652:fructose 2,6-diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen; D000242:Cyclic AMP; D017853:Phosphotransferases (Alcohol Group Acceptor); D025481:Phosphofructokinase-2