Hypothermia blacks β-catenin degradation after focal ischemia in rats

Dephosphorylated and activated glycogen synthase kinase (GSK) 3 beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3 and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3 beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3 beta dephosphorylation. Because hypothermia. reduces infarction, these results contradict with previous studies showing that GSK 3 dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3 beta protein. Corresponding to GSK 3 activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia. (c) 2008 Elsevier B.V. All rights reserved.