NF-κB-Associated MnSOD induction protects against β-amyloid-induced neuronal apoptosis

• Published in: Journal of molecular neuroscience 2006-07, Vol.29 (3), p.279-288
• Main Authors: Sompol, Pradoldej, Xu, Yong, Ittarat, Wanida, Daosukho, Chotiros, Clair, Daret St
• Format: Article
• Language: English
• ISSN: 0895-8696; 1559-1166; 0895-8696
• DOI: 10.1385/JMN:29:3:279

Expression of manganese superoxide dismutase (MnSOD), a nuclear-encoded mitochondrial primary antioxidant enzyme, is protective against various paradigms of oxidative stress-induced brain injury. We have shown previously that the presence of an intronic nuclear factor site, κB (NF-κB), in the MnSOD gene is essential for the induction of MnSOD by tumor necrosis factor α (TNF-α). However, whether activation of NF-κB is protective against oxidative stress-induced neuronal injury is unclear. In the present study, we demonstrate that TNF-α activates NF-κB activity in neuronal, SH-SY5Y, cells and preferentially enhances the binding of p50 and p65 to the promoter/enhancer regions of the MnSOD gene. Binding of NF-κB members to the MnSOD gene leads to the induction of MnSOD mRNA and protein levels. Consequently, induction of MnSOD by TNF-α primes neuronal cells to develop resistance against subsequent exposure to β-amyloid and FeSO . Taken together, these results suggest that NF-κB might exert its protective function by induction of MnSOD leading to subsequent protection against oxidative stress-induced neuronal injury.