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

作者：Nomura Koji; Lee Mercede; Banks Christina; Lee Graham; Morris Brian J^*

来源：Neuroscience Letters, 2013, 549: 163-167.

DOI：10.1016/j.neulet.2013.05.045

• Reactive oxygen species
• MAP kinase
• Apoptosis
• Neurons

Reactive oxygen species (ROS) are believed to be involved in many forms of neurodegeneration, including ischaemic infarct damage and Alzheimer%26apos;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 TAXI 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.

• 出版日期2013-8-9