title: NF-κB activation by peroxynitrite through IκBα-dependent phosphorylation versus nitration in colon cancer cells.
abstract: BACKGROUND
  Peroxynitrite has been proposed to activate Nuclear Factor κappa beta (NF-κB) in a non-canonical or aberrant pathway and to contribute to pathology of many diseases.
  
  
  METHODS
  The activation of NF-κB by peroxynitrite was assessed by Western blot, immunoprecipitation, RT-PCR, and image stream analysis.
  
  
  RESULTS
  Our work showed that in HT-29 cancer cells, peroxynitrite can cause nitration of Inhibitory protein kappa B alpha (IκBα) at the expense of its phosphorylation. This led to a decrease in the degradation and re-synthesis of IκBα. Similar findings were observed for mRNA levels assessed by RT-PCR. Exposure of HT-29 cells to p38 inhibitor SB202190, prior to stimulation, resulted in a dramatic decrease of IκBα kinase and IκBα phosphorylation and caused an increase of peroxynitrite-mediated nitration of IκBα, indicating that peroxynitrite may activate NF-κB via dual mechanism of IκBα phosphorylation which is p38 dependent, as well as IκBα nitration.
  
  
  CONCLUSIONS
  Our findings demonstrate a possible interaction of the p38 pathway with the NF-κB pathway under peroxynitrite stimulation.
authors: Department of Anatomy and Cell Biology, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: Einat
authors: E
authors: Gochman
authors: Jamal
authors: J
authors: Mahajna
authors: Abraham Z
authors: AZ
authors: Reznick