HYPOXIA-ISCHEMIA INDUCES ENDOSOMAL-LYSOSOMAL ALTERATION IN RAT BRAIN

ASENSIO J, ; TRONCOSO M, ; SOSA MA; SELTZER A, , SAAVEDRA JM.; ASENSIO J, ; TRONCOSO M, ; SOSA MA; SELTZER A, , SAAVEDRA JM.

Mendoza

Congreso; XXXIV Reunión Científica 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-lysosomal dysfunction participates in neuronal death as a response to excitotoxicity. In this work, we proposed to study the effect of neonatal hypoxia-ischemia (H/I) on compartimentalization of CatD and Psap. Seven-days old Wistar-Kyoto rat pups were subjected to H/I treatment by ligature of the left carotid artery followed by a short exposure to 100% N2. After 96h, the brain was dissected and both hemispheres from cerebral cortex (Cx) and hippocampus (HIP). CatD, Psap and Lamp-1 (lysosome marker) proteins were evaluated 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 could correspond to a cleavage fragment of LAMP-1. We concluded that H/I induce an increase of cytosolic CatD and Psap due to Lamp-1 cleavage and higher lysosomal-endosomal permeabilization. This phenomenon could be responsible of the excitotoxic damage.