Neuronal lysosome permeabilization dynamics in ischemia

Abstract

The mechanism in which lysosomes are damaged by free radicals during neuronal ischemia is examined in rat hippocampus. There are two hypotheses. The free radicals can degrade the lysosome membrane through liquefaction; all of the intralysosomal proteins would be able to penetrate the membrane, albeit at slower rates for larger proteins. The second mechanism is that pores are created; the proteins within the lysosome that are smaller than the pores can escape while those larger than the pores would not due to the robust nature of the undamaged membrane. Acid Phosphatase (67kda) and Beta-Galactosidase (540 kDa) has been identified as rat intralysosomal neuronal proteins that can be detected as proxies for leakage. Our initial results indicate that the damage undergoes the pore mechanism of damage based on preferential acid phosphatase leakage.