Inhibition of IkappaBalpha phosphorylation prevents glutamate-induced NF-kappaB activation and neuronal cell death

Acta Neurochir Suppl. 2005;93:59-63. doi: 10.1007/3-211-27577-0_8.

Abstract

NF-kappaB is a nuclear transcription factor involved in the control of fundamental cellular functions including regulation of cell survival. We investigated NF-kappaB activation induced by two opposing modulators of cell viability: IL-1beta and glutamate. We found that IL-1beta activated p50, p65 and c-Rel subunits of NF-kappaB, 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-1beta induced the expression of the short anti-apoptotic isoform of Caspase-2. Finally, we analysed the effect of the inhibition of IkappaBalpha degradation on glutamate-induced toxicity by using BAY 11-7082, a selective inhibitor of IkappaBalpha phosphorylation. Our results suggest that BAY 11-7082 preserves neuron viability from the glutamate-mediated injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors
  • Glutamic Acid / pharmacology*
  • I-kappa B Proteins / antagonists & inhibitors
  • I-kappa B Proteins / metabolism*
  • Interleukin-1 / pharmacology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Interleukin-1
  • NF-kappa B
  • Nfkbia protein, rat
  • NF-KappaB Inhibitor alpha
  • Glutamic Acid