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.
Tanaka
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S
Molecular Neurobiology Laboratory, Division of Biological Sciences, Graduate School of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo 060-0810, Japan. shtanaka@sci.hokudai.ac.jp
Koike
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T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology*
D015220:Calcium Channels; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D002118:Calcium