Selective disruption of cadherin/catenin complexes by oxidative stress in precision-cut mouse liver slices

Monika Schmelz, Vanessa J. Schmid, Alan R. Parrish

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Previous work has shown that chemically induced oxidative stress disrupts the protein interactions of the E-cadherin/β-catenin/α-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 β-catenin and γ-catenin; thus four distinct complexes mediate cell-cell adhesion in the liver: E-cadherin/β-catenin/α-catenin, E-cadherin/γ-catenin/α-catenin, N-cadherin/β-catenin/α-catenin, and N-cadherin/γ-catenin/α-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 ♂; 6 h) or tertbutylhydroperoxide (5-50 μM; 6 h). A polyclonal antibody against β- or γ-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:β-catenin co-immunoprecipitation was seen, interactions between β-catenin and N-cadherin were not disrupted by chemical challenge. In addition, no effect on protein interactions of γ-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 β-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/β-catenin complexes in the liver. This response is dictated, in part, by the protein composition of the cell-adhesion complex.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalToxicological Sciences
Volume61
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Cadherin
  • Catenin
  • Oxidative stress
  • Precision-cut liver slices

ASJC Scopus subject areas

  • Toxicology

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