Respiration-dependent H2O2 Removal in Brain Mitochondria via the Thioredoxin/Peroxiredoxin System

We demonstrate that rat brain mitochondria remove H2O2 in a unique respiration-dependent manner primarily via the Trx/ Prx system

Derek A. Drechsel; Manisha Patel

2010

Scholarcy highlights

  • Species,2 including superoxide, H2O2, and hydroxyl radical
  • Measurement/Characterization of Brain Mitochondrial H2O2 Removal via Polarography—A polarographic method that quantitatively measures steady-state H2O2 levels in realtime was utilized to determine whether exogenous H2O2
  • Using a novel polarographic method in this study, we were able to assess an overlooked aspect of reactive oxygen species metabolism, the ability of brain mitochondria to remove H2O2 under physiological conditions
  • Four major findings emerge from this work: 1) brain mitochondria are capable of scavenging exogenous H2O2 under biologically relevant conditions in a respiration-dependent manner, suggesting important roles for this organelle in antioxidant defense against both intra- and extra-mitochondrial ROS sources and as a regulator of cell signaling and redox-dependent processes; 2) in contrast to previous literature, we demonstrate that Trx/ Prx is the major contributing enzyme system to respirationdependent H2O2 removal in brain mitochondria, whereas GSH/GPx and non-enzymatic systems show only minor contributions; 3) inhibition of Trx-dependent antioxidant systems exacerbates H2O2 production by PQ, an environmental neurotoxicant; and 4) partial Trx-dependent removal of H2O2 occurs in intact dopaminergic neurons
  • In contrast to fluorometric methods, polarography does not require the addition of reagents that may alter the system by generating artificial reactions that do not normally occur in the cellular environment
  • We can conclude that TrxR-dependent pathways account for up to 80%
  • Polarography is capable of measuring steady-state, dynamic changes in net H2O2 resulting from both production and/or removal in real-time, whereas fluorometry is typically limited to the measurement of a single aspect of H2O2 metabolism
  • Given that near complete inhibition of TrxR in N27 cells showed only a moderate decrease in H2O2 removal rates, it seems likely that the effects on H2O2 metabolism resulting from specific inhibition of the mitochondrial Trx/Prx system may be difficult to reliably quantify in intact cells

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