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 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.
Tong
L
L
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston 77555-0652, USA.
Werrbach-Perez
K
K
Perez-Polo
J R
JR
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*
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