1. Academic Validation
  2. Ethanol induces necroptosis in gastric epithelial cells in vitro

Ethanol induces necroptosis in gastric epithelial cells in vitro

  • J Food Biochem. 2021 Apr;45(4):e13692. doi: 10.1111/jfbc.13692.
Jianning Liu 1 2 Meng Guo 1 Xiaotong Fan 1
Affiliations

Affiliations

  • 1 State Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, China.
  • 2 Xi'an Gaoxin No. 1 High School, Xi'an, China.
Abstract

The stomach frequently suffers from acute gastric diseases after excessive ingestion of high-concentration alcoholic beverages, but little is known about the pathological mechanism by which ethanol affects the gastric mucosa. The aim of this study was to explore the mechanism of gastric epithelial cell death induced by relatively high concentrations of ethanol in vitro. Ethanol was demonstrated to induce rapid cell death in a concentration-dependent manner (Spearman r = .943, p = .017) and to activate the phosphorylation of key mediators in Necroptosis pathway without influencing the key mediators in Apoptosis pathway. The receptor-interacting serine-threonine kinase 1 (RIP1) kinase inhibitor necrostatin-1s (nec-1s) was found to reverse necroptotic cell death (from 65.5% necrosis to 35.8% necrosis, p = .006) and to inhibit the formation of necrosome complexes. These results indicate Necroptosis rather than Apoptosis pathway is an essential mechanism and is a novel therapeutic target in acute alcoholic gastric diseases. PRACTICAL APPLICATIONS: Alcohol consumption is related with a variety of diseases in many organs, but its pathological mechanism might be quite different due to the exposure extent between the stomach and other organs. Although there have been plenty of studies on alcoholic liver diseases and those in other organs, the pathological mechanism of alcoholic gastric diseases has been poorly investigated. Considering the unique distribution of ethanol on gastric mucosa, it is worthwhile to explore the specific cell death pattern of gastric epithelial cells under high-concentration ethanol treatment. Further investigation of the mechanisms of alcoholic gastric diseases would provide potential therapeutic strategies for the treatment of acute alcoholic gastric diseases as well as other acute alcoholic diseases.

Keywords

almagate; cell death; ethanol; gastric epithelial cell; gastritis; necroptosis.

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