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

Pradoldej Sompol, Yong Xu, Wanida Ittarat, Chotiros Daosukho, Daret St. Clair

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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 FeSO 4. 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.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalJournal of Molecular Neuroscience
Volume29
Issue number3
DOIs
StatePublished - Jul 2006

Bibliographical note

Funding Information:
This work was supported by NIH grants CA049797 and AG05119 to D. S. and by the Royal Golden Jubilee Research Fellowship (The Thailand Research Fund) to P. S. We thank Dr. Jeffrey N. Keller for the SH-SY5Y cells and Edgardo R. Dimayuga for his assistance with the SH-SY5Y cells.

Keywords

  • Apoptosis
  • MnSOD
  • NF-κB
  • SH-SY5Y
  • TNF-α

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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