title: Anisomycin uses multiple mechanisms to stimulate mitogen-activated protein kinases and gene expression and to inhibit neuronal differentiation in PC12 phaeochromocytoma cells.
abstract: Treatment of PC12 cells with nerve growth factor (NGF) stimulates extracellular signal-regulated kinases (ERKs), as well as stress-activated c-Jun N-terminal kinases (JNKs) and p38 kinase, and induces neuronal differentiation. While the pivotal role of ERKs in NGF-induced morphological differentiation is well established, the contribution of JNK- and p38-pathways is less clear. The role of the JNK- and p38-pathway in PC12 cells was analysed by using anisomycin, a protein synthesis inhibitor that activates JNKs and p38. Non-toxic concentrations of anisomycin were found to stimulate these enzyme activities as well as the expression of the early response genes c-jun, c-fos and zif268, and to inhibit NGF-induced neurite formation. These effects of anisomycin appear to be mediated by the generation of reactive oxygen species (ROS), which in turn act through both TrkA/Ras-dependent and -independent signalling pathways. In addition, cross-talk between the p38- and ERK-pathways appears to play a role in the action of anisomycin.
authors.affiliation: Department of Biology, University Medical School of Pécs, H-7643 Pécs, Szigeti 12, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Törocsik
authors.forename: J
authors.initials: J
authors.lastname: Szeberényi
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D018384:Oxidative Stress; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004791:Enzyme Inhibitors; D007093:Imidazoles; D017874:Immediate-Early Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011725:Pyridines; D017382:Reactive Oxygen Species; D020800:Receptor, Nerve Growth Factor; D014157:Transcription Factors; D000841:Anisomycin; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins; C093642:SB 203580