Lq. Tong et al., Prolonged activation of transcription factor AP-1 during NGF-mediated rescue from apoptotic cell death in PC12 cells, NEUROCHEM R, 24(11), 1999, pp. 1431-1441
Rat pheochromocytoma (PC12) cells exhibit apoptotic cell death when deprive
d of serum and can be rescued by nerve growth factor (NGF). We characterize
d AP-1 DNA binding activity in PC12 cells after serum deprivation in the pr
esence or absence of NGF or other neurotrophic agents. There was a decline
in AP-1 DNA binding activity concomitant with apoptosis in PC12 cells after
serum deprivation. Treatment of serum-deprived PC12 with NGF induced persi
stent AP-I binding activity that was blocked by the Trk receptor inhibitor
K252a. PC12 cells treated with dibutyryl cyclic AMP or insulin also display
ed increased AP-I DNA binding activity. While NGF somewhat increased c-Fos
and c-Jun protein levels transiently, it had a more robust and persistent s
timulatory effect on Jun B protein levels. AP-1 transcriptional activity in
creased after NGF, dibutyryl cAMP, or insulin treatment under serum free co
nditions. Curcumin, which inhibits AP-1 activity, blocked the NGF-mediated
rescue. These results would suggest that the rescue of serum-deprived PC12
cells from apoptosis requires increasing endogenous levels of specific Fos/
Jun components of AP-1.