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

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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.

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Authors and Affiliations

  1. Graduate Center for Toxicology, University of Kentucky, 40536, Lexington, KY

    Pradoldej Sompol, Yong Xu, Chotiros Daosukho & Daret St. Clair

  2. Faculty of Medical Technology, Mahidol University, 10700, Bangkok, Thailand

    Pradoldej Sompol, Wanida Ittarat & Chotiros Daosukho

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  1. Pradoldej Sompol
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  2. Yong Xu
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  3. Wanida Ittarat
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Correspondence to Daret St. Clair.

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Sompol, P., Xu, Y., Ittarat, W. et al. NF-κB-Associated MnSOD induction protects against β-amyloid-induced neuronal apoptosis. J Mol Neurosci 29, 279–288 (2006). https://doi.org/10.1385/JMN:29:3:279

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  • DOI: https://doi.org/10.1385/JMN:29:3:279

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