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

Yeste-Velasco, Marc; Folch, Jaume; Jimenez, Andres; Rimbau, Victor; Pallas, Merce; Camins, Antoni

Abstract

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

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Título según WOS: ID WOS:000257187600014 Not found in local WOS DB
Título de la Revista: EUROPEAN JOURNAL OF PHARMACOLOGY
Volumen: 588
Número: 2-3
Editorial: ELSEVIER SCIENCE BV
Fecha de publicación: 2008
Página de inicio: 239
Página final: 243
DOI:

10.1016/j.ejphar.2008.04.019

Notas: ISI