TY - JOUR
T1 - Chemically induced oxidative stress disrupts the E-cadherin/catenin cell adhesion complex
AU - Parrish, Alan R.
AU - Catania, Jeffrey M.
AU - Orozco, Jason
AU - Gandolfi, A. Jay
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - E-cadherin
KW - Liver slices
KW - Oxidative stress
KW - Phosphotyrosine
KW - α-Catenin
KW - β-catenin
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U2 - 10.1093/toxsci/51.1.80
DO - 10.1093/toxsci/51.1.80
M3 - Article
C2 - 10496679
AN - SCOPUS:0032843849
VL - 51
SP - 80
EP - 86
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -