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-3beta 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 beta-catenin markedly degraded at 24 and 48 h 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-3beta. In conclusion, beta-catenin degraded after stroke, and its degradation was caspase-3 dependent.
Zhang
Hanfeng
H
Department of Neurosurgery, Stanford University, Stanford, California 94305-5327, USA.
Gao
Xuwen
X
Yan
Zhimin
Z
Ren
Chuancheng
C
Shimohata
Takayoshi
T
Steinberg
Gary K
GK
Zhao
Heng
H
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000378:metabolism*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3