Enhanced depolarization-evoked calcium signal and reduced [ATP]/[ADP] ratio are unrelated events induced by oxidative stress in synaptosomes

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Abstract

Oxidative insult elicited by hydrogen peroxide (H2O2) was previously shown to increase the basal intracellular Ca2+ concentration in synaptosomes. In the present study, the effect of H2O2 on the depolarization-evoked [Ca2+] signal was investigated. Pretreatment of synaptosomes with H2O2 (0.1-1 mM) augmented the [Ca2+] rise elicited by high K+ depolarization with essentially two alterations, the sudden sharp rise of [Ca2+](i) due to K+ depolarization is enhanced and, instead of a decrease to a stable plateau, a slow, steady rise of [Ca2+](i) follows the peak [Ca2+](i) H2O2 in the same concentration range lowered the ATP level and the [ATP]/[ADP] ratio. When carbonyl cyanide p- (trifluoromethoxy)phenylhydrazone (FCCP) (1 μM) or rotenone (2 μM)/oligomycin (10 μM) was applied initially to block mitochondrial ATP production, the lowered [ATP]/[ADP] ratio was further reduced by subsequent addition of 0.5 mM H2O2. The decline of the [ATP]/[ADP] ratio was parallel with but could not explain the enhanced K+-evoked [Ca2+](i) signal, indicated by experiments in which the [ATP]/[ADP] ratio was decreased by FCCP (0.1 μM) or rotenone (2 μM) to a similar value as by H2O2 without causing any alteration in the [Ca2+], signal. These results indicate that H2O2- evoked oxidative stress, in its early phase, gives rise to a complex dysfunction in the Ca2+ homeostasis and, parallel with it, to an impaired energy status.

Original languageEnglish
Pages (from-to)2529-2537
Number of pages9
JournalJournal of neurochemistry
Volume69
Issue number6
DOIs
Publication statusPublished - Dec 1997

Keywords

  • Energy state
  • Hydrogen peroxide
  • Intracellular Ca concentration
  • Oxidative stress
  • Synaptosomes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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