Inhibiting caspase-3 activity blocks beta-catenin degradation after focal ischemia in rat

Beta-catenin can be cleaved by caspase-3 or degraded by activated glycogen synthase kinase-3 beta via phosphorylating beta-catenin. We tested the hypothesis that beta-catenin undergoes degradation after stroke, and its degradation is dependent on caspase activity. Stroke was generated by permanent middle cerebral artery occlusion and 1 h of transient bilateral common carotid artery occlusion in rats. Active caspase-3 was expressed in the ischemic cortex from 5 to 48 h after stroke, whereas P-catenin markedly degraded at 24 and 48h after stroke. The caspase 3-specific inhibitor, Z-DQMD-FMK, attenuated beta-catenin degradation, but it did not affect phosphorylation of both beta-catenin and glycogen synthase kinase-3 beta. In conclusion, beta-catenin degraded after stroke, and its degradation was caspase-3 dependent.