Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+

Peroxiredoxins (PRDXs) are a family of peroxidases well conserved throughout evolution. Human PRDX3 and PRDX5, two mitochondrial PRDXs, have been implicated in several pathologies associated with oxidative stress. However, the individual role of PRDX3 and PRDX5 in cellular antioxidant defense has never been well established due to their overlapping peroxidatic activities. We investigated the expression and function of mitochondrial PRDXs in human neuroblastoma SH-SY5Y cells. Our results show that PRDX3 and PRDX5 are expressed constitutively in these neuronal cells. To examine further the function of mitochondrial PRDXs, we silenced the expression of PRDX3 and/or PRDX5 using small hairpin RNAs. Our results show that mitochondrial PRDX-depleted cells are more prone to oxidative damages and apoptosis induced by MPP+, a complex I inhibitor which provides an experimental paradigm of Parkinson's disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.