Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in rat striatum.

The present study investigated the role of lysosomal enzymes in excitotoxic neuronal damage induced by excessive stimulation of non-NMDA glutamate receptors with kainic acid (KA). Internucleosomal DNA fragmentation was induced after intrastriatal administration of KA 1.25-5.0 nmol to rats. Increased expression of cathepsin B (P < 0.01, n = 6) but not cathepsin L in KA-injected striatum was observed 12 to 24 h after intrastriatal infusion of KA (2.5 nmol). Treatment with intrastriatal infusion of the cathepsin B inhibitor Z-FA-FMK (5-10 microg) 10 min prior to or 3 h after KA injection robustly attenuated KA-induced (2.5 nmol) DNA fragmentation. Z-FA-FMK (10 microg) also significantly reduced the size of striatal lesions induced by KA (P < 0.01, n = 6). These results suggest that lysosomal enzyme cathepsin B plays an important role in excitotoxic neuronal injury.