Effect of glycolysis inhibition on mitochondrial function in rat brain

J Biochem Mol Toxicol. 2012 May;26(5):206-11. doi: 10.1002/jbt.21404. Epub 2012 Apr 26.

Abstract

Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Brain* / drug effects
  • Brain* / enzymology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • Glycolysis* / drug effects
  • Iodoacetates / pharmacology
  • Lipid Peroxidation / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria* / drug effects
  • Mitochondria* / enzymology
  • Oxygen Consumption / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Iodoacetates
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Glyceraldehyde-3-Phosphate Dehydrogenases