Affordable Access

deepdyve-link
Publisher Website

Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

Authors
  • Chen, Wei-Yang1
  • Wang, Min2
  • Zhang, Jingwen2
  • Barve, Shirish S3
  • McClain, Craig J4
  • Joshi-Barve, Swati5
  • 1 Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; Alcohol Research Center, University of Louisville, Louisville, Kentucky.
  • 2 Alcohol Research Center, University of Louisville, Louisville, Kentucky; Department of Medicine, University of Louisville, Louisville, Kentucky; Hepatobiology and Toxicology Center, University of Louisville, Louisville, Kentucky.
  • 3 Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; Alcohol Research Center, University of Louisville, Louisville, Kentucky; Department of Medicine, University of Louisville, Louisville, Kentucky; Hepatobiology and Toxicology Center, University of Louisville, Louisville, Kentucky.
  • 4 Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; Alcohol Research Center, University of Louisville, Louisville, Kentucky; Department of Medicine, University of Louisville, Louisville, Kentucky; Hepatobiology and Toxicology Center, University of Louisville, Louisville, Kentucky; Department of Medicine, Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky.
  • 5 Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; Alcohol Research Center, University of Louisville, Louisville, Kentucky; Department of Medicine, University of Louisville, Louisville, Kentucky; Hepatobiology and Toxicology Center, University of Louisville, Louisville, Kentucky. Electronic address: [email protected]
Type
Published Article
Journal
American Journal Of Pathology
Publisher
Elsevier
Publication Date
Dec 01, 2017
Volume
187
Issue
12
Pages
2686–2697
Identifiers
DOI: 10.1016/j.ajpath.2017.08.015
PMID: 28935573
Source
Medline
License
Unknown

Abstract

Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease.

Report this publication

Statistics

Seen <100 times