6-hydroxydopamine-induced nuclear factor-kappa B activation in PC12 cells

The involvement of nuclear Factor-kappa B (NF-kappa B) transcription factor in PC12 cell death triggered by the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) was investigated. Results show that oxidative stress generated by 6-OHDA activates NF-kappa B. When the NF-kappa B activation was inhibit...

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Bibliographic Details
Published in:Biochemical pharmacology 2001-08, Vol.62 (4), p.473
Main Authors: Blum, D, Torch, S, Nissou, M F, Verna, J M
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Drug Interactions
Minor Histocompatibility Antigens
Nerve Degeneration - metabolism
NF-kappa B - metabolism
Oxidative Stress - drug effects
Oxidopamine - pharmacology
PC12 Cells - drug effects
PC12 Cells - metabolism
Plant Extracts - pharmacology
Protective Agents - pharmacology
Proteins - pharmacology
Proto-Oncogene Proteins c-bcl-2 - pharmacology
Rats
Reactive Oxygen Species - metabolism
Sesquiterpenes - pharmacology
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Summary:The involvement of nuclear Factor-kappa B (NF-kappa B) transcription factor in PC12 cell death triggered by the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) was investigated. Results show that oxidative stress generated by 6-OHDA activates NF-kappa B. When the NF-kappa B activation was inhibited by parthenolide, PC12 cell death induced by 6-OHDA was significantly increased, thus suggesting an involvement of this transcription factor in a protective mechanism against 6-OHDA toxicity. To further assess this hypothesis, we studied the involvement of NF-kappa B in the protective effect of two anti-apoptotic genes, bcl-2 and bfl-1. Although Bcl-2 and Bfl-1 expression normally protects PC12 cells from 6-OHDA, parthenolide strongly decreased the beneficial effects afforded by transgene expression. These results suggest: (1) that the transcription factor NF-kappa B is likely associated with the protection of catecholaminergic PC12 cells and (2) that the protective effects afforded by bcl-2 and bfl-1 expression may be dependent on NF-kappa activation.
ISSN:0006-2952