Deoxycholic Acid Could Induce Apoptosis and Trigger Gastric Carcinogenesis on Gastric Epithelial Cells by Quantitative Proteomic Analysis.

Yanyan Shi,Ye Wang,Ting Zhang,Shigang Ding,Ying Wei,Jing Zhang

doi:10.1155/2016/9638963

Abstract

Background. Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. Bile reflux has been generally considered to be associated with intestinal metaplasia and gastric cancer. However, the pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown. Methods. To explore the mechanisms by which bile acids induce gastric mucosal lesions, we examined cell apoptosis in the gastric epithelial cell line GES-1 and investigated the changes in protein profiles of GES-1 cells in response to a bile acid deoxycholic acid using a proteomics approach. Changes in the profiles of the differently expressed proteins were analyzed using the DAVID and STRING programs. Results. We found apoptosis was significantly induced in GES-1 cells by deoxycholic acid. Using liquid chromatographic/tandem mass spectrometric (LC-MS/MS) methods, 134 upregulated proteins and 214 downregulated proteins were identified in the bile acid treated GES-1 cells. Bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins. Conclusion. These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa.

Highlights

Reflux of bile is one of the main etiological factors in the pathophysiological processes leading to gastric mucosal lesions in patients with chronic gastritis [1]
An apoptosis detection kit was used to detect apoptosis induced by a 400 μM final concentration of deoxycholic acid in GES-1 cells
Our results showed that deoxycholic acid could induce apoptosis in gastric mucosa cell lines GES-1 and AGS, and the latter cell line AGS was used to avoid the cell-specific effects

Summary

Introduction

Reflux of bile is one of the main etiological factors in the pathophysiological processes leading to gastric mucosal lesions in patients with chronic gastritis [1]. Physiological duodenogastric refluxate does not contain bile acids but only contains HCO3− and IgA, which might have protective functions for gastric mucosa [2]. Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids, and high concentration of bile acids may play a critical role in the induction of intestinal metaplasia (IM) in the stomach. Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. The pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown. These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa

Methods

Results

Discussion

Conclusion