Tretter L, Chinopoulos C, Adam-Vizi V
Department of Medical Biochemistry, Semmelweis University of Medicine, Budapest, Hungary.
J Neurochem. 1997 Dec;69(6):2529-37. doi: 10.1046/j.1471-4159.1997.69062529.x.
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 microM) or rotenone (2 microM)/oligomycin (10 microM) 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 microM) or rotenone (2 microM) to a similar value as by H2O2 without causing any alteration in the [Ca2+]i 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.
