Antioxidant cytoprotection of peroxisomal peroxiredoxin-5

Peroxiredoxin-5 (PRDX5) is a thioredoxin peroxidase which reduces hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. This enzyme is present in the cytosol, mitochondria, peroxisomes and the nucleus in human cells. Antioxidant cytoprotective functions have been previously documented for cytosolic, mitochondrial and nuclear mammalian PRDX5. However, the exact function of PRDX5 in peroxisomes is still not clear. The aim of this work was to determine the function of peroxisomal PRDX5 in mammalian cells, and more specifically in glial cells. In order to study the role of PRDX5 in peroxisomes, the endogenous expression of PRDX5 in murine oligodendrocyte 158N cells was silenced by RNA interference. In addition, human PRDX5 was also overexpressed in peroxisomes using a vector coding for human PRDX5 whose unconventional peroxisomal targeting sequence 1 (PTS1; SQL) was replaced by the prototypical PTS1 SKL. Stable 158N clones were obtained. Antioxidant cytoprotective function of peroxisomal PRDX5 against peroxisomal and mitochondrial KillerRed-mediated ROS production as well as H2O2 was examined using MTT viability assays, roGFP2 and C11-BOBIPY probes. Altogether our results show that peroxisomal PRDX5 protects 158N oligodendrocytes against peroxisomal and mitochondrial KillerRed- and H2O2-induced oxidative stress.publisher: Elsevier articletitle: Antioxidant cytoprotection by peroxisomal peroxiredoxin-5 journaltitle: Free Radical Biology and Medicine articlelink: http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.032 content_type: article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe