title: A study of the relative importance of the peroxiredoxin-, catalase-, and glutathione-dependent systems in neural peroxide metabolism.
abstract: Cells are endowed with several overlapping peroxide-degrading systems whose relative importance is a matter of debate. In this study, three different sources of neural cells (rat hippocampal slices, rat C6 glioma cells, and mouse N2a neuroblastoma cells) were used as models to understand the relative contributions of individual peroxide-degrading systems. After a pretreatment (30 min) with specific inhibitors, each system was challenged with either H₂O₂ or cumene hydroperoxide (CuOOH), both at 100 μM. Hippocampal slices, C6 cells, and N2a cells showed a decrease in the H₂O₂ decomposition rate (23-28%) by a pretreatment with the catalase inhibitor aminotriazole. The inhibition of glutathione reductase (GR) by BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) significantly decreased H₂O₂ and CuOOH decomposition rates (31-77%). Inhibition of catalase was not as effective as BCNU at decreasing cell viability (MTT assay) and cell permeability or at increasing DNA damage (comet test). Impairing the thioredoxin (Trx)-dependent peroxiredoxin (Prx) recycling by thioredoxin reductase (TrxR) inhibition with auranofin neither potentiated peroxide toxicity nor decreased the peroxide-decomposition rate. The results indicate that neural peroxidatic systems depending on Trx/TrxR for recycling are not as important as those depending on GSH/GR. Dimer formation, which leads to Prx2 inactivation, was observed in hippocampal slices and N2a cells treated with H₂O₂, but not in C6 cells. However, Prx-SO₃ formation, another form of Prx inactivation, was observed in all neural cell types tested, indicating that redox-mediated signaling pathways can be modulated in neural cells. These differences in Prx2 dimerization suggest specific redox regulation mechanisms in glia-derived (C6) compared to neuron-derived (N2a) cells and hippocampal slices.
authors: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors: Péricles Arruda
authors: PA
authors: Mitozo
authors: Luiz Felipe
authors: LF
authors: de Souza
authors: Gecioni
authors: G
authors: Loch-Neckel
authors: Samira
authors: S
authors: Flesch
authors: Angelica Francesca
authors: AF
authors: Maris
authors: Cláudia Pinto
authors: CP
authors: Figueiredo
authors: Adair Roberto Soares
authors: AR
authors: Dos Santos
authors: Marcelo
authors: M
authors: Farina
authors: Alcir Luiz
authors: AL
authors: Dafre
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010545:Peroxides / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001555:Benzene Derivatives; D010545:Peroxides; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D002374:Catalase; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione; C007164:cumene hydroperoxide