Activation of protein kinase C delays apoptosis of nerve growth factor-deprived rat sympathetic neurons through a Ca(2+)-influx dependent mechanism.

The effects of protein kinase C (PKC) activation on apoptosis depend on the cell type and on the isoenzymes activated. We show that the apoptosis of nerve growth factor (NGF)-deprived rat sympathetic neurons is delayed for about 24 h by treatment with O-tetradecanoylphorbol 13-acetate (TPA). The cell death was estimated by both morphological changes and the release of a cytoplasmic enzyme into the medium. The PKC inhibitor bisindolylmaleimide inhibited the TPA-mediated delay of neuronal death. The effect of TPA was abolished in conditions of Ca(2+)-free or in the presence of both Ca(2+)/calmodulin-dependent protein kinase II and phosphatidylinositol 3-kinase inhibitors, but was not blocked by either an L- or N-type Ca(2+) channel inhibitor. These results suggest that the survival of the NGF-deprived neurons may be supported by PKC activation followed by Ca(2+) influx.