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

Authors: Sompol, Pradoldej¹; Xu, Yong¹; Ittarat, Wanida²; Daosukho, Chotiros¹; Clair, Daret³

Source: Journal of Molecular Neuroscience, Volume 29, Number 3, July 2006 , pp. 279-288(10)

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Abstract:

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 FeSO₄. 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.

Keywords: MnSOD; TNF-α; NF-κB; SH-SY5Y; apoptosis

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:29:3:279

Affiliations: 1: Graduate Center for Toxicology, University of Kentucky, 40536, Lexington, KY, 2: Faculty of Medical Technology, Mahidol University, 10700, Bangkok, Thailand, 3: Graduate Center for Toxicology, University of Kentucky, 40536, Lexington, KY, Email: dstcl00@uky.edu

Publication date: 2006-07-01