Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Chattopadhyay, Rima; Dyukova, Elena; Singh, Nikhlesh K.; Ohba, Masaaki; Mobley, James A.; Rao, Gadiparthi N.

doi:10.1074/jbc.m113.528190

Cited by 52 publications

(60 citation statements)

References 66 publications

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“…However, most of these studies were focused on epithelial TJs, and therefore, the role of phosphorylation of TJ proteins in the preservation or perturbation of endothelial TJ integrity and its barrier function has not been well-studied. In this context, a few studies, including ours, showed that phosphorylation of TJ proteins leads to endothelial TJ disruption and loss of its barrier function ( 20,21,42,43 ). In the present study, we have extended our previous observations on the role of tyrosine phosphorylation of TJ proteins in the disruption of TJ integrity and barrier function to JamA.…”

Section: Xo-dependent Ros Production Mediates 15(s)-heteinduced Jama supporting

confidence: 75%

“…Previous work from our laboratory showed that 15(S)-HETE, the 15-lipoxygenase (LO) metabolite of arachidonic acid (AA), disrupts EC TJs causing an increase in its barrier permeability ( 20,21 ). We also found that 15(S)-HETE increases XO activity in macrophages ( 22 ).…”

Section: Mass Spectroscopysupporting

confidence: 57%

“…TJs play a crucial role in the maintenance of EC barrier function ( 3,4 ). Previously, we have reported that 15(S)-HETE increases EC barrier permeability by promoting threonine and tyrosine phosphorylation of ZO1 and ZO2, respectively, and their dissociation from TJ complexes ( 20,21 ). In the present study, we examined the role of transmembrane proteins, JamA and occludin, that are present in the TJ complexes in 15(S)-HETE-induced EC barrier disruption.…”

Section: (S)-hete Induces Tyrosine Phosphorylation Of Jama In the Dmentioning

confidence: 99%

“…Endothelial transmigration was measured as described previously ( 21 ). Whenever adenoviral vectors were used, HUVECs were transduced with the control or the indicated adenovirus prior to seeding onto the transwell.…”

Section: Transmigrationmentioning

confidence: 99%

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12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Chattopadhyay

Tinnikov

Dyukova

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org surface to the circulating blood, and releases vasoactive substances involved in the regulation of vascular tone ( 1, 2 ). Besides, it selectively permits the movement of molecules into and out of the bloodstream, and this semipermeable capacity of the endothelial monolayer depends majorly on cell-to-cell connections, namely adherens junctions (AJs), tight junctions (TJs), and gap junctions ( 3, 4 ). Disruption of these junctions leads to a leaky endothelial barrier, which allows the traffi cking of leukocytes through the blood vessels into the interstitial space and initiates infl ammation ( 2, 4 ). A large body of evidence indicates that TJs of endothelium play a pivotal role in modulating its barrier permeability, and dysfunctional endothelium often manifests increased barrier permeability ( 5, 6 ). Many studies suggest that oxidative stress is one of the underlying factors in endothelial dysfunction and atherosclerosis ( 7,8 ). NADPH oxidase, a major source of reactive oxygen species (ROS) production ( 9 ), has been reported to increase EC barrier permeability ( 10, 11 ). Xanthine oxidase (XO), a purine-catabolizing enzyme, was also found as another major source of cellular ROS production ( 12 ). XO results from sulfhydryl oxidation or proteolytic conversion of xanthine dehydrogenase (XDH) ( 13,14 ). Although both XDH and XO convert hypoxanthine and xanthine to uric acid, XO preferentially converts molecular oxygen to superoxide anion and hydrogen peroxide ( 12 ). However, under the reduced state, XDH can also react with molecular oxygen and generate ROS ( 15 ). Although the physiological signifi cance of XDH conversion to XO is not clear, XO was found to be abundantly present in several tissues, including in the luminal surface of the microvascular endothelium, and is thought to be involved in the pathogenesis of various diseases such as infl ammation and Endothelium, which is constituted by a monolayer of endothelial cells (ECs), is the inner most lining of the blood vessels, provides nonplatelet adherent nonthrombotic Abstract To understand the mechanisms of 15(S)-HETEinduced endothelial cell (EC) barrier dysfunction, we examined the role of xanthine oxidase (XO). 15(S)-HETE induced

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Section: Xo-dependent Ros Production Mediates 15(s)-heteinduced Jama supporting

confidence: 75%

Section: Mass Spectroscopysupporting

confidence: 57%

Section: (S)-hete Induces Tyrosine Phosphorylation Of Jama In the Dmentioning

confidence: 99%

Section: Transmigrationmentioning

confidence: 99%

See 2 more Smart Citations

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Chattopadhyay

Tinnikov

Dyukova

et al. 2015

Journal of Lipid Research

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“…For example, claudin-3 phosphorylation at T192, which is mediated by PKA, disturbs the barrier function of tight junctions (D'Souza et al, 2005); phosphorylation of T770 or T772 of ZO-1 leads to its disassembly from tight junctions and affects the endothelial barrier permeability (Chattopadhyay et al, 2014). However, to date, there are limited studies referring to the phosphorylation sites of claudin-4.…”

Section: Discussionmentioning

confidence: 98%

Claudin-4 is required for modulation of paracellular permeability by muscarinic acetylcholine receptor in epithelial cells

Cong

Zhang

et al. 2015

Journal of Cell Science

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The epithelial cholinergic system plays an important role in water, ion and solute transport. Previous studies have shown that activation of muscarinic acetylcholine receptors (mAChRs) regulates paracellular transport of epithelial cells; however, the underlying mechanism is still largely unknown. Here, we found that mAChR activation by carbachol and cevimeline reduced the transepithelial electrical resistance (TER) and increased the permeability of paracellular tracers in rat salivary epithelial SMG-C6 cells. Carbachol induced downregulation and redistribution of claudin-4, but not occludin or ZO-1 (also known as TJP1). Small hairpin RNA (shRNA)-mediated claudin-4 knockdown suppressed, whereas claudin-4 overexpression retained, the TER response to carbachol. Mechanistically, the mAChR-modulated claudin-4 properties and paracellular permeability were triggered by claudin-4 phosphorylation through ERK1/2 (also known as MAPK3 and MAPK1, respectively). Mutagenesis assay demonstrated that S195, but not S199, S203 or S207, of claudin-4, was the target for carbachol. Subsequently, the phosphorylated claudin-4 interacted with β-arrestin2 and triggered claudin-4 internalization through the clathrin-dependent pathway. The internalized claudin-4 was further degraded by ubiquitylation. Taken together, these findings suggested that claudin-4 is required for mAChR-modulated paracellular permeability of epithelial cells through an ERK1/2, β-arrestin2, clathrin and ubiquitin-dependent signaling pathway.

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An Accessible Organotypic Microvessel Model Using iPSC‐Derived Endothelium

Ingram

Hind

Jiminez-Torres

et al. 2017

Adv Healthcare Materials

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While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)-derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell-derived endothelium for the generation of a functional microvessel model is demonstrated. High precision structural and microenvironmental control afforded by the design approach synergizes with the advantages of iPSC to produce microvessels for modeling endothelial biology in vitro. iPSC microvessels show endothelial characteristics, exhibit barrier function, secrete angiogenic and inflammatory mediators, and respond to changes in the extracellular microenvironment by altering vessel phenotype. Importantly, when deployed in the investigation of neutrophils during innate immune recruitment, the presence of the iPSC endothelial vessel facilitates neutrophil extravasation and migration toward a chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic models to open the way for improved and increasingly accessible in vitro tissue, disease, and patient-specific models.

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Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Cited by 52 publications

References 66 publications

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Claudin-4 is required for modulation of paracellular permeability by muscarinic acetylcholine receptor in epithelial cells

An Accessible Organotypic Microvessel Model Using iPSC‐Derived Endothelium

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