Mitochondrial targeted Catalase as a potential antioxidant tool to revert oxidative stress in DS human fibrobasts.

ZAMPONI EMILIANO; HELGUERA PABLO; QUASSOLLO GONZALO; PIGINO GUSTAVO

Workshop; Ciencia & Vida, Cell Biology Summer cuorse.; 2016

The free radical theory of aging propose that cumulative damage caused by reactive oxygen species ROS is responsible of the functional decline of living systems, leading to diseases and eventually death. A successful longevity murine model was designed based on these concepts, targeting over expression peroxide degrading enzyme catalase to mitochondria (mCAT), the main center of reactive oxygen species (ROS) production.Our group has been studying aging in Down syndrome (DS). We have described for DS cells chronic oxidative stress associated with mitochondrial dysfunction that ends up compromising cellular functions, associated to transcriptome showint active antioxidant systems Nrf2 pathway, a master regulator of antioxidant response elements (ARE).Here we are presenting the characterization of mCAT expression in DS cells, using a lentiviral system. The strategy was efficient in decreasing mitochondrial chronic oxidative damage, restoring mitochondrial membrane potential and recovering the organelle's structure in these cells. We observed that mitochondrial dysfunction affected DS fibroblasts migration capacity and that mCAT rescued this parameter, too. Finally we explored Nrf2 pathway activation in DS fibroblasts, confirmed its upstream regulators, and observed that mCAT activity impacted the cellular stress response diminishing Nrf2 stabilization and nuclear translocation.