An ASK1-p38 signalling pathway mediates hydrogen peroxide-induced toxicity in NG108-15 neuronal cells

Nomura, K. , Lee, M., Banks, C., Lee, G. and Morris, B.J. (2013) An ASK1-p38 signalling pathway mediates hydrogen peroxide-induced toxicity in NG108-15 neuronal cells. Neuroscience Letters, 549, pp. 163-167. (doi:10.1016/j.neulet.2013.05.045)

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Abstract

Reactive oxygen species (ROS) are believed to be involved in many forms of neurodegeneration, including ischaemic infarct damage and Alzheimer's disease. Despite the known involvement of p38 and JNK MAP kinases in mediating apoptosis and cell death in a variety of cell types, the details of the signalling pathways activated in neuronal cells by ROS are poorly characterised. Recently TAK1 (MAP3K7), a kinase upstream of JNK and p38, has attracted attention as a possible mediator of ischaemic cell death. This study tested the hypothesis that hydrogen peroxide (H2O2), which produces ROS, induces apoptosis in the NG108-15 neuronal cell line via activation of either TAK1 or the related kinase ASK1 (MAP3K5). H2O2 caused a concentration-dependent reduction in cell viability associated with caspase 3 activation. Loss of cell viability was inhibited by a selective caspase 3 inhibitor, and by the p38 inhibitor SB203580, but was not affected by the JNK inhibitor SP600125. The selective TAK1 inhibitor 5Z-7-oxozeaenol (5Z-7) exacerbated the loss of cell viability, whereas the ASK1 inhibitor NQDI-1 completely prevented caspase activation and cell death. These results show that pharmacological inhibition of ASK1 is neuroprotective, implicating an ASK1-p38 signalling pathway in ROS-induced apoptosis in neurones. The results also imply that the role of TAK1 may be neuroprotective rather than pro-degenerative.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nomura, Koji and Lee, Mr Graham and Morris, Professor Brian
Authors: Nomura, K., Lee, M., Banks, C., Lee, G., and Morris, B.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Neuroscience Letters
Publisher:Elsevier
ISSN:0304-3940

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