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. 2002 Dec 1;368(Pt 2):471–481. doi: 10.1042/BJ20011804

Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress.

Radhakrishna K Rao 1, Shyamali Basuroy 1, Vijay U Rao 1, Karl J Karnaky Jr 1, Akshay Gupta 1
PMCID: PMC1222996  PMID: 12169098

Abstract

The oxidative-stress-induced alteration in paracellular junctional complexes was analysed in Caco-2 cell monolayer. Oxidative stress induced a rapid increase in tyrosine phosphorylation of occludin, zonula occludens (ZO)-1, E-cadherin and beta-catenin. An oxidative-stress-induced decrease in transepithelial electrical resistance was associated with a redistribution of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the intercellular junctions. Genistein, a tyrosine kinase inhibitor, prevented the oxidative-stress-induced decrease in resistance and redistribution of protein complexes. Occludin, ZO-1, E-cadherin and beta-catenin in the Triton-insoluble cytoskeletal fraction were reduced by oxidative stress, which was prevented by genistein. Oxidative stress also reduced the co-immunoprecipitation of ZO-1 with occludin, which was prevented by genistein. Co-immunoprecipitation of beta-catenin with E-cadherin was unaffected by oxidative stress or genistein. ZO-1, E-cadherin and beta-catenin in the plasma membrane or membrane-cytoskeleton were either slightly reduced or unaffected by oxidative stress or genistein. These results show that oxidative stress induces tyrosine phosphorylation and cellular redistribution of occludin-ZO-1 and E-cadherin-beta-catenin complexes by a tyrosine-kinase-dependent mechanism.

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Selected References

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