Neuronal cell death induced by antidepressants: lack of correlation with Egr-1, NF-κB and extracellular signal-regulated protein kinase activation

摘要: Abstract The tricyclic antidepressants (TCA) amitriptyline and desipramine the serotonin reuptake inhibitor fluoxetine induce, at μM concentrations, cell death in HT22 immortalized hippocampal neurons PC12 pheochromocytoma cells. Here, we show that these neurotoxic effects are accompanied by a selective activation of extracellular signal-regulated protein kinase (ERK), biosynthesis transcription factor Egr-1 an increase transcriptional activity NF-κB. However, impairment both ERK MAP kinase-1 (MEK-1) PD98059 did not block death. Moreover, stimulation phosphorylation sphingosine-1-phosphate induce death, indicating signaling pathway required for neuronal induced antidepressants. Likewise, attenuation antidepressant-induced NF-κB elevation intracellular cAMP concentration or retroviral driven expression non-degradable superrepressor IκBαS32A/S36A demonstrated amitriptyline, is integral part apoptotic cascade triggered compounds.