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Anisomycin uses multiple mechanisms to stimulate mitogen‐activated protein kinases and gene expression and to inhibit neuronal differentiation in PC12 phaeochromocytoma cells
Author(s) -
Töro"csik Beáta,
Szeberényi József
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00933.x
Subject(s) - anisomycin , p38 mitogen activated protein kinases , microbiology and biotechnology , kinase , mapk/erk pathway , nerve growth factor , neurite , mitogen activated protein kinase , signal transduction , protein kinase a , biology , chemistry , biochemistry , receptor , in vitro
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.