Glutamate-mediated activation of protein kinase C in hippocampal neurons

Exposure of cultured neurons to glutamate results in the activation of protein kinase C (PKC). However, the mechanisms of this activation process are incompletely understood. To investigate PKC activation in cultured rat hippocampal neurons, we have exposed these cells to 500 microM glutamate for 5 min prior to determination of PKC phosphotransferase activity and protein levels. We observe that PKC activity increases in the membrane fractions by 3.7-fold, but is unchanged in the cytosol. Protein levels are also significantly increased by 5.5-fold in the membrane fractions. These results indicate that in hippocampal neurons, activation of PKC by glutamate does not occur solely by the translocation of PKC from the cytosol to the membrane. We suggest that neurotoxic concentrations of glutamate activate PKC in a translocation-independent manner which may serve as a mediator for glutamate-induced neurotoxicity.