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Neuroprotective Effects of SB-415286 on Hydrogen Peroxide-Induced Cell Death in B65 Rat Neuroblastoma Cells and Neurons

Neuroprotective Effects of SB-415286 on Hydrogen Peroxide-Induced Cell Death in B65 Rat Neuroblastoma Cells and Neurons

Javier G Pizarro, Marc Yeste-Velasco, Victor Rimbau, Gemma Casadesús, Mark A Smith, Mercè Pallàs, Jaume Folch, Antoni Camins

Int J Dev Neurosci. May-Jun 2008;26(3-4):269-76.

PMID: 18342477

Abstract:

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). H(2)O(2) 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 H(2)O(2) (1mM). 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 H(2)O(2) damage. Furthermore, inhibition of GSK-3 activity was not involved in this protective effect.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP264218237	SB 415286		264218-23-7	Price

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