title: Activation of transcription factor AP-1 by extracellular ATP in PC12 cells.
abstract: We have previously shown that extracellular ATP caused cell death in PC12 cells through activation of its receptors. Oxidative stress has been implicated as a mechanism of cell death caused by extracellular ATP. In the present study we examined the possible signal transduction cascades leading to cell death by extracellular ATP. We found, using the electrophoretic mobility shift assay, that transcription factor AP-1 DNA binding activity was stimulated by extracellular ATP. Northern blot analysis showed that mRNA levels of c-fos, c-jun were elevated after treatment with ATP. The stimulation was receptor mediated, since it was blocked by the ATP receptor antagonist, suramin. The stimulated AP-1 binding was also blocked by the antioxidant N-acetyl-L-cysteine, indicating that reactive oxygen species generated following ATP stimulation were involved in the induction of AP-1 activity. It appears that both translational and posttranslational events contributed to the increased AP-1 DNA binding since cyclohexamide (a protein synthesis inhibitor), genistein (tyrosine kinase inhibitor) and staurosporine (PKC inhibitor) each partially blocked the AP-1 activation. Changes in AP-1 DNA binding activity may modulate expression of target genes involved in cell death pathways.
authors.affiliation: Dept. of Pharmacology, University of Missouri, Columbia 65212, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: A Y
authors.initials: AY
authors.lastname: Sun
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016762:Genes, fos; D016758:Genes, jun; D018384:Oxidative Stress; D016716:PC12 Cells / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D013498:Suramin; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D000111:Acetylcysteine