title: The contribution of thioredoxin-2 reductase and glutathione peroxidase to H(2)O(2) detoxification of rat brain mitochondria.
abstract: Brain mitochondria are not only major producers of reactive oxygen species but they also considerably contribute to the removal of toxic hydrogen peroxide by the glutathione (GSH) and thioredoxin-2 (Trx2) antioxidant systems. In this work we estimated the relative contribution of both systems and catalase to the removal of intrinsically produced hydrogen peroxide (H(2)O(2)) by rat brain mitochondria. By using the specific inhibitors auranofin and 1-chloro-2,4-dinitrobenzene (DNCB), the contribution of Trx2- and GSH-systems to reactive oxygen species (ROS) detoxification in rat brain mitochondria was determined to be 60±20% and 20±15%, respectively. Catalase contributed to a non-significant extent only, as revealed by aminotriazole inhibition. In digitonin-treated rat hippocampal homogenates inhibition of Trx2- and GSH-systems affected mitochondrial hydrogen peroxide production rates to a much higher extent than the endogenous extramitochondrial hydrogen peroxide production, pointing to a strong compartmentation of ROS metabolism. Imaging experiments of hippocampal slice cultures showed on single cell level substantial heterogeneity of hydrogen peroxide detoxification reactions. The strongest effects of inhibition of hydrogen peroxide removal by auranofin or DNCB were detected in putative interneurons and microglial cells, while pyramidal cells and astrocytes showed lower effects. Thus, our data underline the important contribution of the Trx2-system to hydrogen peroxide detoxification in rat hippocampus. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Alexei P
authors.initials: AP
authors.lastname: Kudin
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Augustynek
authors.forename: Anja Kerstin
authors.initials: AK
authors.lastname: Lehmann
authors.forename: Richard
authors.initials: R
authors.lastname: Kovács
authors.forename: Wolfram S
authors.initials: WS
authors.lastname: Kunz
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001310:Auranofin / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007202:Indicators and Reagents / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D004137:Dinitrochlorobenzene; D007202:Indicators and Reagents; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; C516113:Txn2 protein, rat; D001310:Auranofin; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione; D004072:Digitonin