Document Detail


Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett's esophagus.
MedLine Citation:
PMID:  18617556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We hypothesized that, in esophageal squamous epithelial cells, there are differences among individuals in the signal transduction pathways activated by acid reflux that might underlie the development of Barrett's esophagus. To explore that hypothesis, we immortalized nonneoplastic, esophageal squamous cells from patients with gastroesophageal reflux disease (GERD) with (NES-B3T) and without (NES-G2T) Barrett's esophagus and used those cells to study acid effects on MAPK proteins. During endoscopy in patients with GERD with and without Barrett's esophagus, we took biopsy specimens from the distal squamous esophagus to study MAPK proteins before and after esophageal perfusion with 0.1 N HCl. We used immunoblotting and Western blotting to study MEK1/2 phosphorylation at two activating sites (serines 217/221), MEK1 phosphorylation at an inhibitory site (threonine 286), and MEK1/2 activity. After acid exposure, both cell lines exhibited increased MEK1/2 phosphorylation at the activating sites; the NES-B3T cells had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the NES-G2T cells showed an acid-induced increase in MEK1/2 activity. Similarly, in the squamous epithelium of patients with GERD with and without Barrett's esophagus, acid perfusion increased MEK1/2 phosphorylation at the activating sites in both patient groups; the Barrett's patients had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the patients without Barrett's demonstrated an acid-induced increase in ERK1/2 phosphorylation. In esophageal squamous cell lines and biopsies from patients with GERD with and without Barrett's esophagus, we have found differences in MAPK pathways activated by acid exposure. We speculate that these differences might underlie the development of Barrett's metaplasia.
Authors:
Hui Ying Zhang; Xi Zhang; Xi Chen; Deena Thomas; Kathy Hormi-Carver; Frederick Elder; Stuart J Spechler; Rhonda F Souza
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-07-10
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  295     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-10     Completed Date:  2008-10-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G470-8     Citation Subset:  IM    
Affiliation:
Department of Medcine, Veterans Affairs North tExas Health Care System and the University of Texas Southwestern Medical School, MC# 111B1, Dallas VA Medical Ctr., 4500 South Lancaster Rd., Dallas, TX 75216, USA.
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MeSH Terms
Descriptor/Qualifier:
Barrett Esophagus / enzymology*,  etiology,  pathology
Cell Line, Transformed
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Disease Progression
Dual Specificity Phosphatase 1 / metabolism
Epithelial Cells / drug effects,  enzymology*,  pathology,  radiation effects
Esophagoscopy
Esophagus / drug effects,  enzymology*,  pathology,  radiation effects
Gastric Acid / metabolism
Gastroesophageal Reflux / complications,  enzymology*,  pathology
Humans
Hydrochloric Acid / pharmacology
MAP Kinase Kinase 1 / metabolism
MAP Kinase Kinase 2 / metabolism
MAP Kinase Signaling System* / drug effects,  radiation effects
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Mitogen-Activated Protein Kinases / metabolism*
Phosphorylation
Time Factors
Tumor Suppressor Protein p53 / metabolism
Ultraviolet Rays
Grant Support
ID/Acronym/Agency:
DK63621/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 7647-01-0/Hydrochloric Acid; EC 2.7.1.-/MAP2K1 protein, human; EC 2.7.1.-/MAP2K2 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 2; EC 3.1.3.48/DUSP1 protein, human; EC 3.1.3.48/Dual Specificity Phosphatase 1
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