Hydrogen peroxide induces a long-lasting inhibition of the Ca(2+)-dependent glutamate release in cerebrocortical synaptosomes without interfering with cytosolic Ca2+.
We studied the action of H2O2 on the exocytosis of glutamate by cerebrocortical synaptosomes. The treatment of synaptosomes with H2O2 (50-150 microM) for a few minutes results in a long-lasting depression of the Ca(2+)-dependent exocytosis of glutamate, induced by KCl or by the K(+)-channel inhibitor 4-aminopyridine. The energy state of synaptosomes, as judged by the level of phosphocreatine and the ATP/ADP ratio, was not affected by H2O2, although a transient decrease was observed after the treatment. H2O2 did not promote peroxidation, as judged by the formation of malondialdehyde. In indo-1-loaded synaptosomes, the treatment with H2O2 did not modify significantly the KCl-induced increase of [Ca2+]i. H2O2 inhibited exocytosis also when the latter was induced by increasing [Ca2+]i with the Ca2+ ionophore ionomycin. The effects of H2O2 were unchanged in the presence of superoxide dismutase and the presence of the Fe3+ chelator deferoxamine. These results appear to indicate that H2O2, apparently without damaging the synaptosomes, induces a long-lasting inhibition of the exocytosis of glutamate by acting directly on the exocytotic process.
Zoccarato
F
F
Department of Biological Chemistry, University of Padova, Italy.
Valente
M
M
Alexandre
A
A
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism*; D013997:Time Factors
D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D002118:Calcium