Involvement of autophagic and lysosomal pathways under manganese-induced oxidative stress in microglial cells

PORTE ALCON, S.; KOTLER, M. L.; ALAIMO, A.; GOROJOD, R. M.

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

Manganese (Mn) overexposure causes a neurodegenerative disease known as Manganism. It has been reported that Mn activates the microglia triggering the production of inflammatory mediators (ROS/RNS and TNF-α) which could promote neuronal death. In this context, the proper elimination of dead cells by microglia is crucial. This phagocytic activity depends on the lysosomal compartment where internalized material is digested. However, under oxidative stress conditions lysosomes are severely affected. As a consequence, the hydrolytic enzymes are released into the cytosol triggering several cell death pathways. We aim to study the role of lysosomes in Mn-induced microglial cell death. Also, the possible activation of the autophagic pathway was assessed. We previously demonstrated that Mn (250 and 750µM; 24h) generates oxidative stress in murine BV2 microglial cells. In the present work lysosomes amount and size were analyzed by Lysotracker Red DND-99 staining (fluorescence microscopy and Flow Cytometry). Results indicated that Mn increases the number of these acidic vesicles (250µM: 147%, p