Activation of protein kinase C-δ attenuates kainate-induced cell death of cortical neurons

We investigated the role of individual protein kinase C (PKC) isoforms during kainate toxicity in cortical neurons. Treatment with 50 μM kainate induced isoform-specific activation of PKC-δ according to the translocation from the soluble to the particulate fraction, while it caused remarkable decreases in PKC α, β, and ζ in both fractions. Kainate-induced neuronal death was significantly increased by pharmacological inhibition of PKC-δ with rottlerin, suggesting a protective role of PKC-δ against kainate toxicity. A PKC activator phorbol 12-myristate 13-acetate remarkably attenuated the kainate-induced neuronal death. Although phorbol 12-myristate 13-acetate activates PKC- and PKC-δ, the protective effect of phorbol 12-myristate 13-acetate was almost completely abolished by rottlerin, but not by V1-2. These results suggest that activation of PKC-δ attenuates the kainate-induced cell death of cortical neurons.