Differential induction of NF-kappaB activity and neural cell death by antidepressants in vitro.
Tricyclic antidepressants and selective serotonin reuptake inhibitors are here shown to induce cell death in a neural cell line. The exposure to these drugs led to increased generation of reactive oxygen species and a concomitant reduction of intracellular glutathione levels. Furthermore, these antidepressants induced DNA fragmentation and increased the transcriptional and DNA-binding activity of NF-kappaB. In contrast, treatment with type A and B monoamine oxidase inhibitors did not induce changes in NF-kappaB activity and did not exert a detrimental influence on cell viability. These results indicate that some antidepressant drugs may cause both oxidative stress and changes in cellular antioxidative capacity, resulting in altered NF-kappaB activity and, ultimately, cell death.
Post
A
A
Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany. post@mpipsykl.mpg.de
Crochemore
C
C
Uhr
M
M
Holsboer
F
F
Behl
C
C
D000818:Animals; D000928:Antidepressive Agents / Q000145:classification / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010545:Peroxides / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D005978:Glutathione; D019803:Glutathione Disulfide; D006861:Hydrogen Peroxide; D008996:Monoamine Oxidase Inhibitors; D016328:NF-kappa B; D010545:Peroxides; D011993:Recombinant Fusion Proteins; D017367:Selective Serotonin Reuptake Inhibitors