Hypoxia-ischemia affects the distribution of lysosomal proteins

TRONCOSO, M.; ASENSIO, J.; CARVELLI, L.; SOSA, M. A.; BANNOUD, N.; SELTZER, A.

Mendoza

Simposio; II Simposio Internacional de Medicina Traslacional; 2019

Facultad de Ciencias Médicas, UNCuyo

Neuronal excitotoxicity induced by glutamatergic receptoroverstimulation contributes to brain damage. Recent studies haveshown that lysosomal membrane permeabilization (LMP) is involvedin ischemia-associated neuronal death. In this study we evaluated theeffect of neonatal hypoxia-ischemia (HI), as a model of excitotoxicity,on the lysosomal integrity throughout the distribution of the lysosomalproteins cathepsin D and prosaposin. Rat pups (7 days old) of theWistar Kyoto strain were submitted to HI and they were euthanized4 days after treatment and the cerebral cortex (Cx) and hippocampus(HIP) were processed for immunohistochemistry or immunoblotting.Treatment induced an increase of gliosis and also a redistribution ofboth prosaposin and cathepsin D (as intermediate and mature forms),into the cytosol of the HIP and Cx. In addition, HI induced a decreaseof LAMP-1 in the membranous fraction and the appearance of areactive band to anti-LAMP-1 in the cytosolic fraction, suggesting acleavage of this protein. From these results, we propose that theabnormal release of Cat D and PSAP to the cytosol is triggered as aresult of LAMP-1 cleavage in HI animals, which leads to cell damage.This could be a common mechanism in pathological conditions thatcompromises neuronal survival and brain function.