Peroxynitrite Inhibits Epidermal Growth Factor Receptor Signaling in Caco-2 Cells

Aliye Uc, Neil W. Kooy, Jeffrey L. Conklin, Warren P. Bishop

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Intestinal mucosa serves as an important barrier that may be disrupted by inflammation. A complex system of cellular and humoral factors, including epidermal growth factor (EGF), maintains the integrity of this barrier. We hypothesized that peroxynitrite, generated in inflamed intestinal epithelium, can alter the EGF receptor function by nitrating tyrosine residues and blocking ligand-activated tyrosine autophosphorylation. Caco-2 cells or A431 cell membranes were treated with peroxynitrite or its decomposed form. Cell proliferation was measured by [3H]thymidine uptake. Immunoblot and immunoprecipitation were used to assess the tyrosine phosphorylation and nitration. Binding of epidermal growth factor to its receptor was detected by affinity labeling with 125I-EGF. Peroxynitrite inhibited EGF-induced Caco-2 cell proliferation and binding of EGF to its receptor in a concentration-dependent manner. Peroxynitrite abolished EGF-stimulated receptor autophosphorylation and nitrated EGF receptor tyrosine residues. Peroxynitrite generated during inflammation may disrupt the EGF-induced signaling in intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)2353-2359
Number of pages7
JournalDigestive Diseases and Sciences
Volume48
Issue number12
DOIs
StatePublished - Dec 1 2003

Keywords

  • Cell signaling
  • Epidermal growth factor
  • Intestinal epithelial cells
  • Nitric oxide
  • Oxidative stress
  • Peroxynitrite

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