Two sides of the same coin: lysosomal and autophagic pathways in manganese-induced glial cell death

GOROJOD R. M.; ALAIMO A.; SAPIENZA C; KOTLER M.L.

Huerta Grande, Provincia de Córdoba, Argentina

Congreso; II Reunión conjunta Taller Argentino de Neurociencias-Sociedad Argentina de Investigación en Neurociencias; 2010

Sociedad Argentina de Neurociencias

Manganese (Mn) overexposure produces neurodegenerative damage associated with a high risk of developing Idiopathic Parkinson’s Disease. There is increasing evidence that autophagy impairment and the subsequent accumulation of aggregated proteins are involved in the pathogenesis of neurodegenerative diseases. In this work we studied the role of the lysosomal/autophagic pathways in Mn-induced Parkinsonism in glioma C6 cells. Cell viability measured by neutral red (a vital dye that accumulates in lysosomes) retention, resulted in a 45±4% (p<0,001) increase after 6h incubation with 750µM Mn in serum free media. Under these conditions, an increase in the autophagic vacuoles size was observed. Wortmannin and PD98059 preincubations prevented Mn effects measured by Neutral Red (10±4%, p>0,05) indicating the possible involvement of different autophagic pathways. Furthermore, we demonstrated the participation of the lysosomal pathway measuring both an increase in lysosomes size (stained with Lysotracker Red), and in cell viability by inhibition of v-ATPase and Cathepsin D activities with Bafilomycin A1 and Pepstatine A, respectively. Our results suggest the involvement of the lysosomal/autophagyc compartment in Mn cytotoxicity and shows a new link between Parkinson´s disease and Manganism.