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Updated: Oct 7, 2026
Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology
Published on: March 14, 2020
Selective disruption of cadherin/catenin complexes by oxidative stress in precision-cut mouse liver slices
M Schmelz1, V J Schmid, A R Parrish
1Department of Pathology, College of Medicine, University of Arizona, Tucson, Arizona, USA.
Abstract:
Previous work has shown that chemically induced oxidative stress disrupts the protein interactions of the E-cadherin/beta-catenin/alpha-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 beta-catenin and gamma-catenin; thus four distinct complexes mediate cell-cell adhesion in the liver: E-cadherin/beta-catenin/alpha-catenin, E-cadherin/gamma-catenin/alpha-catenin, N-cadherin/beta-catenin/alpha-catenin, and N-cadherin/gamma-catenin/alpha-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 microM; 6 h) or tert-butylhydroperoxide (5-50 microM; 6 h). A polyclonal antibody against beta- or gamma-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:beta-catenin co-immunoprecipitation was seen, interactions between beta-catenin and N-cadherin were not disrupted by chemical challenge. In addition, no effect on protein interactions of gamma-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 beta-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/beta-catenin complexes in the liver. This response is dictated, in part, by the protein composition of the cell-adhesion complex.
Insights
Oxidative stress selectively disrupts E-cadherin/beta-catenin complexes in the liver, impacting cell adhesion. This disruption is influenced by the specific protein composition of the cell-adhesion complex.
Area of Science:
- Hepatology
- Cell Biology
- Toxicology
Background:
- Oxidative stress is known to disrupt protein interactions within the E-cadherin/beta-catenin/alpha-catenin complex.
- The liver expresses multiple cadherin/catenin complexes, including E-cadherin and N-cadherin with beta-catenin and gamma-catenin, mediating cell-cell adhesion.
- Previous studies suggest a role for oxidative stress in hepatic cadherin/catenin complex disruption, but the selectivity across different complexes remains unclear.
Purpose of the Study:
- To investigate the impact of chemically induced oxidative stress on distinct cadherin/catenin complexes in precision-cut mouse liver slices.
- To determine if oxidative stress selectively disrupts specific cadherin/catenin interactions in hepatocytes.
- To elucidate the role of protein composition in the response of cell-adhesion complexes to oxidative stress.
Main Methods:
- Precision-cut mouse liver slices were challenged with oxidative agents diamide or tert-butylhydroperoxide.
- Co-immunoprecipitation using antibodies against beta-catenin or gamma-catenin followed by Western-blot analysis for E-cadherin and N-cadherin.
- Indirect immunofluorescence microscopy to assess the co-localization of cadherins and catenins.
Main Results:
- Oxidative stress challenge led to a decrease in E-cadherin:beta-catenin co-immunoprecipitation.
- Interactions between beta-catenin and N-cadherin were not disrupted by chemical challenge.
- No effect was observed on protein interactions involving gamma-catenin with either E-cadherin or N-cadherin.
- Indirect immunofluorescence confirmed a heterogeneous reduction in E-cadherin and beta-catenin co-localization, but not other complexes.
Conclusions:
- Oxidative stress selectively disrupts E-cadherin/beta-catenin complexes in the liver.
- The observed selectivity in disruption is partly determined by the protein composition of the cell-adhesion complex.
- These findings highlight the differential vulnerability of hepatic cell-adhesion complexes to oxidative stress.
