Toxicological Sciences 61, 389-394 (2001)
Copyright © 2001 by the Society of Toxicology
SYSTEMS TOXICOLOGY |
Selective Disruption of Cadherin/Catenin Complexes by Oxidative Stress in Precision-Cut Mouse Liver Slices
,1
* Department of Pathology, College of Medicine, University of Arizona, Tucson, Arizona; and
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, Texas
Previous work has shown that chemically induced oxidative stress disrupts the protein interactions of the E-cadherin/ß-catenin/
-catenin complex in precision-cut mouse liver slices (Parrish et al., 1999, Toxicol. Sci. 51, 80–86). Although these data suggest a role for oxidative stress in disruption of hepatic cadherin/catenin complexes, multiple complexes are co-expressed in the liver. Both E- and N- cadherin are co-expressed in hepatocytes, as well as ß-catenin and 
-catenin; thus four distinct complexes mediate cell-cell adhesion in the liver: E-cadherin/ß-catenin/-catenin, E-cadherin/-catenin/-catenin, N-cadherin/ß-catenin/-catenin, and N-cadherin/-catenin/-catenin. Taking advantage of the retention of normal organ architecture and cellular heterogeneity offered by precision-cut mouse liver slices, the current study was designed to examine the impact of chemically induced oxidative stress on cadherin/catenin complexes. Precision-cut mouse liver slices were challenged with diamide (25–250 µM; 6 h) or tert-butylhydroperoxide (5–50 µM; 6 h). A polyclonal antibody against ß- or -catenin was used to immunoprecipitate proteins prior to Western-blot analysis with monoclonal antibodies to E- or N-cadherin. Although a decrease in E-cadherin:ß-catenin co-immunoprecipitation was seen, interactions between ß-catenin and N-cadherin were not disrupted by chemical challenge. In addition, no effect on protein interactions of -catenin with either cadherin was observed. Indirect immunofluorescence was used to co-localize catenins and cadherins following chemical challenge. Consistent with the biochemical observations, a heterogeneous reduction in co-localization of E-cadherin and ß-catenin was seen in precision-cut liver slices, but not other cadherin/catenin complexes. Taken together, these data suggest that oxidative stress selectively disrupts E-cadherin/ß-catenin complexes in the liver. This response is dictated, in part, by the protein composition of the cell-adhesion complex.
Key Words: cadherin; catenin; oxidative stress; precision-cut liver slices.
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