Involvement of glycogen synthase kinase-3β in hydrogen peroxide-induced suppression of Tcf/Lef-dependent transcriptional activity

Hydrogen peroxide (H2O2) mediates induction of cytotoxicity in various cell types. GSK-3β has been found to participate in a number of signaling pathways, including cell proliferation and cell death. In the present study, we show that GSK-3β is rapidly dephosphorylated and activated in response to H2O2 treatment. H2O2 also dephosphorylates Akt/PKB in a dose- and time-dependent manner. Overexpression of Akt/PKB attenuates H2O2-induced dephosphorylation of GSK-3β. Ectopic expression of Dvl-1, a component of Wnt signaling, stimulates Akt/PKB and inhibits dephosphorylation of GSK-3β by H2O2. Furthermore, H2O2 causes the reduction of β-catenin level and LiCl-mediated activation of Tcf/Lef-dependent transcription activity. These findings suggest that GSK-3β is involved in H2O2-mediated inhibition of Tcf/Lef-dependent transcriptional activity.