Prolonged activation of transcription factor AP-1 during NGF-mediated rescue from apoptotic cell death in PC12 cells

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.