Chemically induced oxidative stress disrupts the E-cadherin/catenin cell adhesion complex

Alan R. Parrish, Jeffrey M. Catania, Jason Orozco, A. Jay Gandolfi

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The impact of xenobiotics on intercellular adhesion, a fundamental biological process regulating most, if not all, cellular pathways, has been sparsely investigated. Cell-cell adhesion is regulated in the epithelium primarily by the E-cadherin/catenin complex. To characterize the impact of oxidative stress on the E-cadherin/catenin complex, precision-cut mouse liver slices were challenged with two model compounds for the generation of oxidative stress, diamide (DA; 25-250 μM) or t-butylhydroperoxide (tBHP; 5- 50 μM), for 6 h. At the concentrations used, neither compound elicited cytotoxicity, as assessed by intracellular K+ content and leakage of lactate dehydrogenase into the culture media. However, a 25% reduction in non-protein sulfhydryl levels, an indication of oxidative perturbation, was seen in liver slices treated with DA or tBHP. Total protein expression of E-cadherin, β-, or α-catenin was not affected by challenge with DA or tBHP. A decrease of β-catenin in the SDS-soluble fraction of slices, an indicator of the formation of the adhesion complex, was observed. Additionally, a decrease in β-catenin interactions with E-cadherin and α-catenin, as assessed by immunoprecipitation and Western blot analysis, was seen. Disruption of the E- cadherin/catenin complex by tBHP, but not DA, correlated with enhanced tyrosine phosphorylation of β-catenin. These results suggest that noncytotoxic oxidative stress disrupts the E-cadherin/catenin cell adhesion complex in precision-cut mouse liver slices.

Original languageEnglish (US)
Pages (from-to)80-86
Number of pages7
JournalToxicological Sciences
Volume51
Issue number1
DOIs
StatePublished - Sep 28 1999

Keywords

  • E-cadherin
  • Liver slices
  • Oxidative stress
  • Phosphotyrosine
  • α-Catenin
  • β-catenin

ASJC Scopus subject areas

  • Toxicology

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