1. Role of ion transporters in the bile acid-induced esophageal injury.
- Author
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Laczkó D, Rosztóczy A, Birkás K, Katona M, Rakonczay Z Jr, Tiszlavicz L, Róka R, Wittmann T, Hegyi P, and Venglovecz V
- Subjects
- Aged, Aged, 80 and over, Barrett Esophagus pathology, Bile Acids and Salts metabolism, Calcium metabolism, Cell Line, Chloride-Bicarbonate Antiporters metabolism, Epithelial Cells metabolism, Epithelial Cells pathology, Esophageal Mucosa metabolism, Esophageal Mucosa pathology, Female, Gene Expression Regulation, Humans, Hydrogen-Ion Concentration, Inositol Phosphates metabolism, Ion Transport, Male, Membrane Transport Proteins genetics, Metaplasia, Middle Aged, Sodium-Bicarbonate Symporters metabolism, Sodium-Hydrogen Exchangers metabolism, Time Factors, Barrett Esophagus metabolism, Bile Acids and Salts toxicity, Epithelial Cells drug effects, Esophageal Mucosa drug effects, Membrane Transport Proteins metabolism
- Abstract
Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury., (Copyright © 2016 the American Physiological Society.)
- Published
- 2016
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