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Neuroprotective effects of SB‐415286 on hydrogen peroxide‐induced cell death in B65 rat neuroblastoma cells and neurons
Author(s) -
Pizarro Javier G.,
YesteVelasco Marc,
Rimbau Victor,
Casadesús Gemma,
Smith Mark A.,
Pallàs Mercè,
Folch Jaume,
Camins Antoni
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.02.002
Subject(s) - neuroprotection , oxidative stress , reactive oxygen species , gsk 3 , chemistry , neurodegeneration , pharmacology , antioxidant , biochemistry , microbiology and biotechnology , biology , kinase , medicine , disease
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 (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 H 2 O 2 damage. Furthermore, inhibition of GSK‐3 activity was not involved in this protective effect.