Mitochondrial Targeted Catalase reduces Oxidative Stress in DS cells

ZAMPONI E; BUSCIGLIO J; HELGUERA P

Puerto Varas

Congreso; XXVIII ANNUAL MEETING CHILEAN SOCIETY FOR CELL BIOLOGY; 2014

CHILEAN SOCIETY FOR CELL BIOLOGY

Introduction It is widely accepted that the ageing process is associated with progressive accumulation of cellular damage due to Reactive Oxygen Species (ROS), which are mainly generated as a by-product of mitochondrial function. What is not yet clear is the cause of this phenomenon, which could be, among many others, an increase in ROS production or a reduced turn-over by antioxidant enzymes. Certain diseases, like Down Syndrome (DS), show an accelerated rate of ageing and that correlates with increased levels of Oxidative Stress (OS) markers, making it an interesting model to study this process. Our hypothesis is that enhancing the antioxidant activity inside the mitochondria could prevent the accumulation of damage caused by ROS, increasing DS cells viability. Material and Methods We used Mouse Embryonic Fibroblast (MEF) treated with H2O2 to induce OS and human DS cells. We developed a lentiviral vector to target Catalase to the mitochondrial matrix (mCAT). To visualize the results, we employed Western Blot and Confocal Microscopy. Results Lentiviral vector successfully direct Catalase expression to mitochondrial matrix of MEF and DS cells. We observed a decrease of OS markers as well as an increase in viability in mCAT expressing cells, both DS and H2O2-treated MEF. Discussion Our result indicates that mCAT expression is able to promote DS and H2O2-treated cells viability, counteracting the negative effects induced by ROS. These results provide data for the development of new strategies to reduce OS damage in aging and related diseases.