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

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.

Effects of prednisolone on the dystrophin-associated proteins in the blood–brain barrier and skeletal muscle of dystrophic mdx mice

“…[49][50][51] For both occludin and ZO-1, phosphorylation levels help regulate barrier permeability, [52][53][54] and increased paracellular permeability associated with the tyrosine phosphorylation, and dissociation of occludin and ZO-1 from the cytoskeleton can be caused by oxidative stress. 55 Furthermore, vascular endothelial growth factor (VEGF) can increase intercellular permeability by enhancing ZO-1 and occludin phosphorylation, causing displacement and the reduction of ZO-1 expression, 56,57 corroborating the role of a tyrosine kinasedependent mechanism for the association of the junctional complex to cytoskeleton. Accordingly, in the brain of mdx mice, some vascular permeability is recognizable due to alteration of TJs, such as the detachment of their external leaflet membrane, altered expression of claudin-1 and ZO-1, and increased phosphorylation of ZO-1.…”

Dietary phenylalanine-improved intestinal barrier health in young grass carp (Ctenopharyngodon idella) is associated with increased immune status and regulated gene expression of cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules

“…ROS-induced disruption of TJ proteins by reducing the ZO-1 and occludin complex in Caco-2 cell monolayers has been reported [66]. Meanwhile, ROS can induce lipid and protein oxidative damage to destroy the integrity of epithelial cells in the intestine of Jian carp [7].…”

“…Previous studies have indicated that decreased expression of claudin c [68], claudin 3 [69], claudin 15 [70], occludin and ZO-1 [66] impaired the barrier function. The data presented herein showed that deficiency or excess of Phe downregulated claudin c, claudin 3 and claudin 15, occludin and ZO-1 gene expression, however, those were up-regulated by optimal Phe supplementation in all intestinal segments.…”

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

“…As shown by Hsia et al [12], a probable mechanism by which cSrc promotes invasive behavior is through formation of a transient complex with focal adhesion kinase (FAK), another protein tyrosine kinase [12]. Some evidence suggests that TJ protein phosphorylation plays an important role in the regulation of cell-cell adhesion [13,14]. It is worth noting that occludin and CRB3, intercellular binding proteins, have been used as epithelial and polarity markers in EMT studies [15,16].…”