The role of NF-κB in 6-hydroxydopamine- and TNFα-induced apoptosis of PC12 cells

Victoria Tarabin, Markus Schwaninger*

*Korrespondierende/r Autor/-in für diese Arbeit
27 Zitate (Scopus)

Abstract

6-Hydroxydopamine (6-OHDA) is widely used to study the death of catecholaminergic cells related to Parkinson's disease. Oxidative stress and gene transcription are known to mediate the pro-apoptotic effect of 6-OHDA. As redox mechanisms are involved in activation of the transcription factor NF-κB, we studied the role of NF-κB in 6-OHDA-induced death of PC12 cells. We stably transfected PC12 cells with a doxycycline-regulated expression vector for the NF-KB super-repressor (IκBα mutated at serine-32 and serine-36, IκBα-SR). NF-κB transcriptional activity was evaluated by transient transfection of an NF-κB-driven luciferase reporter gene. Expression of IκBα-SR inhibited NF-κB stimulated by tumor necrosis factor α (TNFα) and 6-OHDA. Apoptosis was quantified by counting cells with condensed nuclei. IκBα-SR inhibited apoptosis induced by 6-OHDA but enhanced apoptosis that was triggered by TNFα. The converse effects of NF-κB could be due to different target genes that are induced in the context of TNFα and 6-OHDA stimulation. Indeed, TNFα stimulated mRNA accumulation of the anti-apoptotic superoxide dismutase 2 through NF-κB whereas 6-OHDA induced mRNA accumulation of the proapoptotic c-myc. These data demonstrate that NF-κB regulates survival of the neuron-like PC12 cells in a stimulus-specific manner. In the context of 6-OHDA stimulation, NF-κB mediates pro-apoptotic effects, suggesting that NF-κB signaling could be a target for drug development in Parkinson-related neurodegeneration.

OriginalspracheEnglisch
ZeitschriftNaunyn-Schmiedeberg's Archives of Pharmacology
Jahrgang369
Ausgabenummer6
Seiten (von - bis)563-569
Seitenumfang7
ISSN0028-1298
DOIs
PublikationsstatusVeröffentlicht - 01.06.2004

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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