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GSK-3β inhibition and prevention of mitochondrial apoptosis inducing factor release are not involved in the antioxidant properties of SB-415286

Abstract:

The antioxidant effects of lithium and SB-415286, two glycogen synthase kinase-3β (GSK-3β) inhibitors, were studied in cerebellar granule neurons by measuring changes in 2, 7-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescence. GSK-3β inhibitors inhibit apoptosis mediated by serum and potassium withdrawal (S/K withdrawal) and GSK-3β activation, as measured by β-catenin degradation. Furthermore, as both drugs prevent mitochondrial apoptosis inducing factor (AIF) release, these data indicate that GSK-3β inhibitors prevent caspase-independent apoptosis in cerebellar granule neurons induced by S/K withdrawal. While the most specific GSK-3β inhibitor, SB-415286, demonstrated antioxidant effects, Li+ 10 mM did not. These results indicate that lithium 10 mM and SB-415286 20 μM exert anti-apoptotic effects in cases of S/K withdrawal mediated by GSK-3β inhibition. However, these antioxidant properties are independent of GSK-3β inhibition and prevention of mitochondrial AIF release. © 2008 Elsevier B.V. All rights reserved.