Role of mitochondrial peroxiredoxin 5 in the control of apoptosis induced by MPP+ in human dopaminergic neuroblastoma SH-SY5Y cells

The contribution of mitochondria to the pathogenesis of neurodegenerative disease such as Parkinson's disease (PD) is ascribed largely to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are obligatory by-products of oxidative phosphorylation. In order to protect themselves from ROS/RNS, cells use non-enzymatic and enzymatic systems including the recently characterized peroxiredoxins (PRDXs). Among them, PRDX5 is a mammalian thioredoxin peroxidase and peroxynitrite reductase ubiquitously expressed in tissues including brain. Here, we investigated the role of mitochondrial PRDX5 in human dopaminergic SH-SY5Y neuronal cells in the control of apoptosis induced by MPP+, a toxin which provides an experimental paradigm of PD. We showed that mitochondrial overexpression of PRDX5 protects SH-SY5Y cells via the modulation of mitochondrial ROS and RNS generated upon MPP+ treatment and, downstream, modulates the regulation of a succession of mitochondrial-mediated molecular events including mitochondrial DNA protection, the decreases of caspase and calpain activities, the control of cytosolic Ca2+ concentration and nuclear condensation. Moreover using RNA inteference, PRDX5-depleted cells were shown to be more sensitive to MPP+. Altogether, these results suggest that mitochondrial PRDX5 may play an important role not only in ROS and RNS scavenging in the mitochondria but also in the redox regulation of mitochondrial apoptosis signaling pathway. In acellular assays, upon exposure to peroxides, we showed that recombinant PRDX5 form complexes with plasmid DNA which is controlled by the redox status of PRDX5. We hypothesized that PRDX5 could act as a stress sensor. Although PRDX5 would function as an antioxidant at low ROS/RNS levels, hyperoxidation of the PRDX5 could result in the reallocation of PRDX5 from mitochondrial matrix antioxidant to DNA-binding protein. In conclusion, this work provides evidence that overexpression of mitochondrial PRDX5 can slow the rate of human neuroblastoma cell degeneration, an effect referred to as neuroprotection. Moreover, depletion of PRDX5 sensitizes SH-SY5Y cells to neurodegeneration. Hence, its role as an antioxidant is strengthened but its function associated with its binding to DNA needs to be further investigated.Doctorat en sciences (sciences biologiques) (BIOL 3)--UCL, 200

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

Diagnostic territorial de la Wallonie

A l’aube de l’actualisation du SDER, la CPDT a reçu la mission de dresser le diagnostic territorial de la Wallonie. Cette publication présente ce diagnostic et s’articule en trois grandes parties.La première partie aborde six défis majeurs pour l'avenir - le défi démographique, le défi climatique, le défi énergétique, le défi de la compétitivité, le défi de la cohésion sociale et le défi de la mobilité- et envisage dans une approche prospective comment le territoire sera impacté par ces changements.La seconde partie du diagnostic vise à estimer les besoins spatiaux des grands secteurs occupant et dynamisant le territoire. Une analyse fine permet de dégager ces besoins sur la base des structures héritées mais aussi d’extrapoler les enjeux de leur adaptation aux grands défis.Dans la troisième partie, le diagnostic se penche sur l’intégration des besoins sectoriels à l’espace wallon. L’examen des dimensions spatiales permet de conclure le diagnostic de manière transversale et territoriale. La première dimension concerne l'insertion de la Wallonie dans l’Europe des Régions et dégage les principaux enjeux vis-à-vis des projets européens et des régions voisines. Une autre dimension a pour objet la structure spatiale interne de la Wallonie et interroge ses pôles et ses aires de pertinences. Enfin, le diagnostic examine la question des spécificités et des relations entre villes et campagnes en Wallonie.0http://cpdt.wallonie.be/publications/diagnostic-territorial-de-la-wallonieinfo:eu-repo/semantics/publishe