Journal article
Peroxynitrite inhibits epidermal growth factor receptor signaling in Caco-2 cells
Digestive diseases and sciences, Vol.48(12), pp.2353-2359
2003
DOI: 10.1023/B:DDAS.0000007874.20403.1d
PMID: 14714624
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.
Details
- Title: Subtitle
- Peroxynitrite inhibits epidermal growth factor receptor signaling in Caco-2 cells
- Creators
- Aliye UC - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, United StatesNeil W KOOY - Department of Pediatrics, University of Cincinnati Medical Center, Cincinnati, Ohio, United StatesJeffrey L CONKLIN - Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United StatesWarren P BISHOP - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Digestive diseases and sciences, Vol.48(12), pp.2353-2359
- Publisher
- Springer; Heidelberg
- DOI
- 10.1023/B:DDAS.0000007874.20403.1d
- PMID
- 14714624
- ISSN
- 0163-2116
- eISSN
- 1573-2568
- Language
- English
- Date published
- 2003
- Academic Unit
- Stead Family Department of Pediatrics; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition
- Record Identifier
- 9984047853002771
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