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Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons
K Shinpo1, S Kikuchi, F Moriwaka
1Department of Neurology, Hokkaido University Hospital, Kita 14, Nishi 5, Kitaku, Sapporo, Japan. kshinpo@med.hokudai.ac.jp
Abstract:
Pretreatments with TNF-alpha and lower concentrations of C2-ceramide protected cultured mesencephalic neurons from excitotoxicity in a dose-dependent manner. These protective effects are reduced by cotreatment with N,N-dimethylsphingosine (DMS), an inhibitor of sphingosine kinase. Since the pretreatment with sphingosine-1-phosphate (SPP) showed a neuroprotective effect, our data suggest that protective effects of TNF and C2-ceramide could be attributable to their further metabolism to SPP.

