scholarly journals Inhibiting Connexin43/Zonula Occludens‐1 Interactions Improves Alcoholic Lung Barrier Function in vivo

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Lauren Jeffers ◽  
Carissa James ◽  
Ryan Reed ◽  
Michael Koval
Keyword(s):  
Barrier Function ◽  
Zonula Occludens ◽  
Zonula Occludens 1

scholarly journals COOH Terminus of Occludin Is Required for Tight Junction Barrier Function in Early Xenopus Embryos

1997 ◽  
Vol 138 (4) ◽  
pp. 891-899 ◽  
Author(s):  
Yan-hua Chen ◽  
Christa Merzdorf ◽  
David L. Paul ◽  
Daniel A. Goodenough
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Barrier Function ◽  
Integral Membrane Protein ◽  
Full Length ◽  
Intercellular Spaces ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
First Time

Occludin is the only known integral membrane protein localized at the points of membrane– membrane interaction of the tight junction. We have used the Xenopus embryo as an assay system to examine: (a) whether the expression of mutant occludin in embryos will disrupt the barrier function of tight junctions, and (b) whether there are signals within the occludin structure that are required for targeting to the sites of junctional interaction. mRNAs transcribed from a series of COOH-terminally truncated occludin mutants were microinjected into the antero–dorsal blastomere of eight-cell embryos. 8 h after injection, the full-length and the five COOH-terminally truncated proteins were all detected at tight junctions as defined by colocalization with both endogenous occludin and zonula occludens-1 demonstrating that exogenous occludin correctly targeted to the tight junction. Importantly, our data show that tight junctions containing four of the COOH-terminally truncated occludin proteins were leaky; the intercellular spaces between the apical cells were penetrated by sulfosuccinimidyl-6-(biotinamido) Hexanoate (NHS-LC-biotin). In contrast, embryos injected with mRNAs coding for the full-length, the least truncated, or the soluble COOH terminus remained impermeable to the NHS-LC-biotin tracer. The leakage induced by the mutant occludins could be rescued by coinjection with full-length occludin mRNA. Immunoprecipitation analysis of detergent-solubilized embryo membranes revealed that the exogenous occludin was bound to endogenous Xenopus occludin in vivo, indicating that occludin oligomerized during tight junction assembly. Our data demonstrate that the COOH terminus of occludin is required for the correct assembly of tight junction barrier function. We also provide evidence for the first time that occludin forms oligomers during the normal process of tight junction assembly. Our data suggest that mutant occludins target to the tight junction by virtue of their ability to oligomerize with full-length endogenous molecules.

scholarly journals Impaired barrier function in patients with house dust mite–induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression

2016 ◽  
Vol 137 (4) ◽  
pp. 1043-1053.e5 ◽  
Author(s):  
Brecht Steelant ◽  
Ricard Farré ◽  
Paulina Wawrzyniak ◽  
Jochen Belmans ◽  
Emily Dekimpe ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
House Dust ◽  
House Dust Mite ◽  
Barrier Function ◽  
Zonula Occludens ◽  
Dust Mite ◽  
Zonula Occludens 1

scholarly journals ZO-1 determines adherens and gap junction localization at intercalated disks

2011 ◽  
Vol 300 (2) ◽  
pp. H583-H594 ◽  
Author(s):  
Joseph A. Palatinus ◽  
Michael P. O'Quinn ◽  
Ralph J. Barker ◽  
Brett S. Harris ◽  
Jane Jourdan ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Ventricular Myocytes ◽  
Dominant Negative ◽  
Cell Junction ◽  
Disease States ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
Intercalated Disks

The disruption of the spatial order of electromechanical junctions at myocyte-intercalated disks (ICDs) is a poorly understood characteristic of many cardiac disease states. Here, in vitro and in vivo evidence is provided that zonula occludens-1 (ZO-1) regulates the organization of gap junctions (GJs) and adherens junctions (AJs) at ICDs. We investigated the contribution of ZO-1 to cell-cell junction localization by expressing a dominant-negative ZO-1 construct (DN-ZO-1) in rat ventricular myocytes (VMs). The expression of DN-ZO-1 in cultured neonatal VMs for 72 h reduced the interaction of ZO-1 and N-cadherin, as assayed by colocalization and coimmunoprecipitation, prompting cytoplasmic internalization of AJ and GJ proteins. DN-ZO-1 expression in adult VMs in vivo also reduced N-cadherin colocalization with ZO-1, a phenomenon not observed when the connexin-43 (Cx43)-ZO-1 interaction was disrupted using a mimetic of the ZO-1-binding ligand from Cx43. DN-ZO-1-infected VMs demonstrated large GJs at the ICD periphery and showed a loss of focal ZO-1 concentrations along plaque edges facing the disk interior. Additionally, there was breakdown of the characteristic ICD pattern of small interior and large peripheral GJs. Continuous DN-ZO-1 expression in VMs over postnatal development reduced ICD-associated Cx43 GJs and increased lateralized and cytoplasmic Cx43. We conclude that ZO-1 regulation of GJ localization is via an association with the N-cadherin multiprotein complex and that this is a key determinant of stable localization of both AJs and GJs at the ICD.

scholarly journals Anisakis simplex products impair intestinal epithelial barrier function and occludin and zonula occludens-1 localisation in differentiated Caco-2 cells

2020 ◽  
Vol 14 (7) ◽  
pp. e0008462
Author(s):  
Noelia Carballeda-Sangiao ◽  
Isabel Sánchez-Alonso ◽  
Alfonso Navas ◽  
Susana C. Arcos ◽  
Pilar Fernández de Palencia ◽  
...  
Keyword(s):  
Barrier Function ◽  
Anisakis Simplex ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Zonula Occludens ◽  
Zonula Occludens 1

scholarly journals The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1192
Author(s):  
Randy E. Strauss ◽  
Louisa Mezache ◽  
Rengasayee Veeraraghavan ◽  
Robert G. Gourdie
Keyword(s):  
Barrier Function ◽  
Therapeutic Potential ◽  
Endothelial Barrier ◽  
Cell Periphery ◽  
Endothelial Barrier Function ◽  
Mimetic Peptide ◽  
Zonula Occludens ◽  
Junction Protein ◽  
Zonula Occludens 1 ◽  
Cell Cell

The Cx43 carboxyl-terminus (CT) mimetic peptide, αCT1, originally designed to bind to Zonula Occludens 1 (ZO1) and thereby inhibit Cx43/ZO1 interaction, was used as a tool to probe the role of Cx43/ZO1 association in regulation of epithelial/endothelial barrier function. Using both in vitro and ex vivo methods of barrier function measurement, including Electric Cell-Substrate Impedance Sensing (ECIS), a TRITC-dextran Transwell permeability assay, and a FITC-dextran cardiovascular leakage protocol involving Langendorff-perfused mouse hearts, αCT1 was found to protect the endothelium from thrombin-induced breakdown in cell–cell contacts. Barrier protection was accompanied by significant remodeling of the F-actin cytoskeleton, characterized by a redistribution of F-actin away from the cytoplasmic and nuclear regions of the cell, towards the endothelial cell periphery, in association with alterations in cellular chiral orientation distribution. In line with observations of increased cortical F-actin, αCT1 upregulated cell–cell border localization of endothelial VE-cadherin, the tight junction protein Zonula Occludens 1 (ZO1), and the Gap Junction Protein (GJ) Connexin43 (Cx43). A ZO1 binding-incompetent variant of αCT1, αCT1-I, indicated that these effects on barrier function and barrier-associated proteins, were likely associated with Cx43 CT sequences retaining ability to interact with ZO1. These results implicate the Cx43 CT and its interaction with ZO1, in the regulation of endothelial barrier function, while revealing the therapeutic potential of αCT1 in the treatment of vascular edema.

scholarly journals Beneficial Effects of Quercetin on Microcystin-LR Induced Tight Junction Defects

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Zhou ◽  
Mei Xue ◽  
Yunfei Jiang ◽  
Miaomiao Zhang ◽  
Changming Wang ◽  
...  
Keyword(s):  
Protein Kinase B ◽  
Transepithelial Electrical Resistance ◽  
Akt Pathway ◽  
Oxygen Species ◽  
Akt Signaling Pathway ◽  
Beneficial Effects ◽  
Zonula Occludens ◽  
Zonula Occludens 1

Quercetin has numerous functions including antioxidant and anti-inflammatory effects. The beneficial effect of quercetin against microcystin-LR (MC-LR)-induced testicular tight junctions (TJs) defects in vitro and in vivo were investigated. Significant reductions in transepithelial electrical resistance, occludin, and zonula occludens-1(ZO-1) levels were detected in the MC-LR-treated TM4 cells, and quercetin attenuated these effects. Interestingly, quercetin suppressed MC-LR-induced phosphorylation of protein kinase B (AKT). It effectively inhibited the accumulation of reactive oxygen species (ROS) in cells stimulated by MC-LR. In addition, ROS inhibitors blocked the TJ damage that is dependent on the AKT signaling pathway induced by MC-LR. In conclusion, our results suggest that alleviates MC-LR-impaired TJs by suppressing the ROS-regulated activation of the AKT pathway.

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