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Inhibition of IκBα phosphorylation prevents glutamate-induced NF-κB activation and neuronal cell death

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Re-Engineering of the Damaged Brain and Spinal Cord

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 93))

Summary

NF-κB is a nuclear transcription factor involved in the control of fundamental cellular functions including regulation of cell survival. We investigated NF-κB activation induced by two opposing modulators of cell viability: IL-1β and glutamate. We found that IL-1β activated p50, p65 and c-Rel subunits of NF-κB, while glutamate activated only p50 and p65 proteins. Cell stimulation by glutamate, correlated with expression of the pro-apoptotic genes Caspase-3, Caspase-2L and Bax. Conversely, IL-1β induced the expression of the short anti-apoptotic isoform of Caspase-2. Finally, we analysed the effect of the inhibition of IκBα degradation on glutamate-induced toxicity by using BAY 11-7082, a selective inhibitor of IκBα phosphorylation. Our results suggest that BAY 11-7082 preserves neuron viability from the glutamate-mediated injury.

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References

  1. Andrews NC, Faller DV (1991) A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleid Acid Res 19: 2499

    Article  CAS  Google Scholar 

  2. Bethea JR, Castro M, Keane RW, Lee TT, Dietrich WD, Yezierski RP (1998) Traumatic spinal cord injury induces nuclear factor-kappaB activation. J Neurosci 18: 3251–3260

    PubMed  CAS  Google Scholar 

  3. Cheema ZF, Wade SB, Sata M, Walsh K, Sohrabji F, Miranda RC (1999) Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB. J Neurosci 19: 1754–1770

    PubMed  CAS  Google Scholar 

  4. Dai Y, Pei XY, Rahmani M, Conrad DH, Dent P, Grant S (2004) Interruption of the NF-{kappa}B pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells. Blood 103(7): 2761–2770

    Article  PubMed  CAS  Google Scholar 

  5. Ferri KF, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3(11): E255–263

    Article  PubMed  CAS  Google Scholar 

  6. Grilli M, Pizzi M, Memo M, Spano PF (1996) Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science 274: 1383–1385

    Article  PubMed  CAS  Google Scholar 

  7. Hsu YT, Wolter KG, Youle RJ (1997) Cytosol-to-membrane redistribution of Bax and Bcl-x(L) during apoptosis. Proc Natl Acad Sci USA 94(8): 3668–3672

    Article  PubMed  CAS  Google Scholar 

  8. Hunot S, Brugg B, Ricard D, Michel PP, Muriel MP, Ruberg M, Faucheux BA, Agid Y, Hirsch EC (1997) Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with Parkinson’s disease. Proc Natl Acad Sci USA 94: 7531–7536

    Article  PubMed  CAS  Google Scholar 

  9. Jones KH, Senft JA (1985) An improved method to determine cell viability by simultaneous staining with fluorescein diacetate-propidium iodide. J Histochem Cytochem 33: 77–79

    PubMed  CAS  Google Scholar 

  10. Kopp E, Ghosh S (1994) Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 265(5174): 956–959

    Article  PubMed  CAS  Google Scholar 

  11. Koulic E, Nguyen T, Johnson K, Giardina CA, D’Mello SR (2001) NFκB is involved in the survival of cerebellar granule neurons: association of IκB phosphorylation with cell survival. J Neurochem 76: 1188–1198

    Article  Google Scholar 

  12. Luo Y, Cao G, Pei W, O’Horo C, Graham SH, Chen J (2002) Induction of caspase-activated deoxyribonuclease activity after focal cerebral ischemia and reperfusion. J Cereb Blood Flow Metab 22(1): 15–20

    Article  PubMed  CAS  Google Scholar 

  13. Mattson MP, Culmsee C, Yu Z, Camandola S (2000) Roles of nuclear factor kappaB in neuronal survival and plasticity. J Neurochem 74: 443–456

    Article  PubMed  CAS  Google Scholar 

  14. Middleton G, Hamanoue M, Enokido Y, Wyatt S, Pennica D, Jaffray E, Hay RT, Davies AM (2000) Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons. J Cell Biol 148: 325–332

    PubMed  CAS  Google Scholar 

  15. O’Neill LA, Kaltschmidt C (1997) NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20: 252–258

    Article  PubMed  CAS  Google Scholar 

  16. Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T, Gerritsen ME (1997) Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem 272(34): 21096–21103

    Article  PubMed  CAS  Google Scholar 

  17. Pizzi M, Fallacara C, Arrighi V, Memo M, Spano PF (1993) Attenuation of excitatory amino acid toxicity by metabotropic glutamate receptor agonists and aniracetam in primary cultures of cerebellar granule cells. J Neurochem 61: 683–689

    Article  PubMed  CAS  Google Scholar 

  18. Pizzi M, Goffi F, Boroni F, Benarese M, Perkins SE, Liou H, Spano PF (2002) Opposing role for NF-κB/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleuki-1β. J Biol Chem 277(23): 20717–20723

    Article  PubMed  CAS  Google Scholar 

  19. Qin ZH, Chen RW, Wang Y, Nakay M, DeMaw C, Chase TN (1999) Nuclear factor κB nuclear translocation upregulates c-Myc and p53 expression during NMDA receptor-mediated apoptosis in rat striatum. J Neurosci 19: 4023–4035

    PubMed  CAS  Google Scholar 

  20. Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M (1999) NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat Med 5: 554–559

    Article  PubMed  CAS  Google Scholar 

  21. Terai K, Matsuo A, McGeer PL (1996b) Enhancement of immunoreactivity for NF-kappa B in the hippocampal formation and cerebral cortex of Alzheimer’s disease. Brain Res 735: 159–168

    Article  PubMed  CAS  Google Scholar 

  22. Wang L, Miura M, Bergeron L, Zhu H, Yuan J (1994) Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell 78(5): 739–750

    Article  PubMed  CAS  Google Scholar 

  23. Yu ZF, Zhou D, Bruce-Keller AJ, Kindy MS, Mattson MP (1999) Lack of the p50 subunit of NF-κB increases vulnerability of hippocampal neurons to excitotoxic injury. J Neurosci 19: 8856–8865

    PubMed  CAS  Google Scholar 

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© 2005 Springer-Verlag

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Pizzi, M., Sarnico, I., Boroni, F., Benetti, A., Benarese, M., Spano, P.F. (2005). Inhibition of IκBα phosphorylation prevents glutamate-induced NF-κB activation and neuronal cell death. In: von Wild, K.R.H. (eds) Re-Engineering of the Damaged Brain and Spinal Cord. Acta Neurochirurgica Supplementum, vol 93. Springer, Vienna. https://doi.org/10.1007/3-211-27577-0_8

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  • DOI: https://doi.org/10.1007/3-211-27577-0_8

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-24150-9

  • Online ISBN: 978-3-211-27577-1

  • eBook Packages: MedicineMedicine (R0)

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