6-hydroxydopamine-induced nuclear factor-kappaB activation in PC12 cells

• Published in: Biochemical pharmacology 2001-08, Vol.62 (4), p.473-481
• Main Authors: Blum, David, Torch, Sakina, Nissou, Marie-France, Verna, Jean-Marc
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Bcl-2; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Medical sciences; NF-kappaB; Parkinson’s disease; PC12 cells; Pharmacology. Drug treatments; Toxicity: nervous system and muscle
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(01)00680-3

The involvement of nuclear Factor-kappaB (NF-κB) 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-κB. When the NF-κB 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-κB 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-κB 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-κ activation.