title: Prolonged activation of transcription factor AP-1 during NGF-mediated rescue from apoptotic cell death in PC12 cells.
abstract: Rat pheochromocytoma (PC12) cells exhibit apoptotic cell death when deprived of serum and can be rescued by nerve growth factor (NGF). We characterized AP-1 DNA binding activity in PC12 cells after serum deprivation in the presence 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 persistent AP-1 binding activity that was blocked by the Trk receptor inhibitor K252a. PC12 cells treated with dibutyryl cyclic AMP or insulin also displayed increased AP-1 DNA binding activity. While NGF somewhat increased c-Fos and c-Jun protein levels transiently, it had a more robust and persistent stimulatory effect on Jun B protein levels. AP-1 transcriptional activity increased after NGF, dibutyryl cAMP, or insulin treatment under serum free conditions. 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.
authors.affiliation: Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston 77555-0652, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tong
authors.forename: K
authors.initials: K
authors.lastname: Werrbach-Perez
authors.forename: J R
authors.initials: JR
authors.lastname: Perez-Polo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D003474:Curcumin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016758:Genes, jun / Q000235:genetics; D026121:Indole Alkaloids; D007328:Insulin / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D016895:Culture Media, Serum-Free; D026121:Indole Alkaloids; D007328:Insulin; D018808:Transcription Factor AP-1; D003994:Bucladesine; D004247:DNA; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D011493:Protein Kinase C; D003474:Curcumin