HYPOXIA-ISCHEMIA INDUCES ENDOSOMAL-LYSOSOMAL ALTERATION IN RAT BRAIN

TRONCOSO M; ASENSIO J; SELTZER A; SOSA MA

Mendoza

Congreso; XXXIII Reunión Anual de la Sociedad de Biología de Cuyo; 2016

Sociedad de Biología de Cuyo

The endosomal-lysosomal system plays an important role in the modulation of the cell integrity. The protease Cathepsin D (CatD)and the protein prosaposin (Psap) participate in neuronal homeostasis. Previous studies have shown that endosomal-lysosomaldysfunction participates in neuronal death as a response to excitotoxicity. In this work, we proposed to study the effect of neonatalhypoxia-ischemia (H/I) on compartimentalization of CatD and Psap. Seven-days old Wistar-Kyoto rat pups were subjected to H/Itreatment by ligature of the left carotid artery followed by a short exposure to 100% N2. After 96h, the brain was dissected andboth hemispheres from cerebral cortex (Cx) and hippocampus (HIP). CatD, Psap and Lamp-1 (lysosome marker) proteins wereevaluated in membranes and cytosols from Cx and HIP by immunoblotting. We observed a significant increase to controls.Moreover, by using anti Lamp-1 we observed a protein of ~50 kDa in the cytosolic fraction of the injured tissue, which couldcorrespond to a cleavage fragment of LAMP-1. We concluded that H/I induce an increase of cytosolic CatD and Psap due toLamp-1 cleavage and higher lysosomal-endosomal permeabilization. This phenomenon could be responsible of the excitotoxicdamage