Neuroprotective effects of SB-415286 on hydrogen peroxide-induced cell death in B65 rat neuroblastoma cells and neurons

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• 作者：Javier G. Pizarro ; Marc Yeste-Velasco ; Victor Rimbau ; Gemma Casadesú ; s ; Mark A. Smith ; Mercè ; Pallà ; s ; Jaume Folch ; Antoni Camins
• 关键词：SB-415286 ; Lithium ; B65 Neuroblastoma cells ; Cerebellar granule cells ; H₂O₂ ; Oxidative stress
• 刊名：International Journal of Developmental Neuroscience
• 出版年：2008
• 出版时间：May-June 2008
• 年：2008
• 卷：26
• 期：3-4
• 页码：269-276
• 全文大小：897 K

文摘

Glycogen synthase kinase-3 (GSK-3) is involved in the pathogenesis of several neurodegenerative diseases. In addition, as oxidative stress has been implicated in all neurodegenerative disorders, the inhibition of both pathways offers a potential strategy for preventing or delaying neurodegeneration. We examined the cytoprotective effects of lithium and SB-415286, two inhibitors of GSK-3, using a rat B65 cell line and also in cerebellar granule cells (CGN). H₂O₂ decreased the inactive form of GSK-3 (phospho-GSK-3 at Ser9), as measured by immunoblot experiments involving an antibody against the inactive form of the enzyme. Moreover, lithium inhibited this effect. While SB-415286 exerted a protective effect, lithium did not attenuate the toxic effects of H₂O₂ (1 mM). We then examined those mechanisms implicated in the protective effects of SB-415286. When we analyzed reactive oxygen species (ROS) production using the fluorescent probe 2,7-dichlorodihydrofluorescein diacetate in B65 cells, as well as in CGN, we found that SB-415286 strongly reduced DCF fluorescence. Lithium, however, did not exhibit any antioxidant properties. We conclude that the GSK-3 inhibitor SB-415286 has antioxidant properties, which may explain the cytoprotective effects against H₂O₂ damage. Furthermore, inhibition of GSK-3 activity was not involved in this protective effect.