scholarly journals NTPDase1 and -2 are expressed by distinct cellular compartments in the mouse colon and differentially impact colonic physiology and function after DSS colitis

2019 ◽  
Vol 317 (3) ◽  
pp. G314-G332 ◽  
Author(s):  
Vladimir Grubišić ◽  
Alberto L. Perez-Medina ◽  
David E. Fried ◽  
Jean Sévigny ◽  
Simon C. Robson ◽  
...  
Keyword(s):  
Barrier Function ◽  
Nucleoside Triphosphate ◽  
Gut Motility ◽  
Epithelial Barrier Function ◽  
Functional Roles ◽  
Dss Colitis ◽  
Health And Disease ◽  
And Function ◽  
Cellular Compartments ◽  
Catalytic Functions

ATP is both an important mediator of physiological gut functions such as motility and epithelial function, and a key danger signal that mediates cell death and tissue damage. The actions of extracellular ATP are regulated through the catalytic functions extracellular nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), -2, -3, and -8, which ultimately generate nucleosides. Ectonucleotidases have distinct cellular associations, but the specific locations and functional roles of individual NTPDases in the intestine are still poorly understood. Here, we tested the hypothesis that differential and cell-selective regulation of purine hydrolysis by NTPDase1 and -2 plays important roles in gut physiology and disease. We studied Entpd1 and Entpd2 null mice in health and following colitis driven by 2% dextran sulfate sodium (DSS) administration using functional readouts of gut motility, epithelial barrier function, and neuromuscular communication. NTPDase1 is expressed by immune cells, and the ablation of Entpd1 altered glial numbers in the myenteric plexus. NTPDase2 is expressed by enteric glia, and the ablation of Entpd2 altered myenteric neuron numbers. Mice lacking either NTPDase1 or -2 exhibited decreased inhibitory neuromuscular transmission and altered components of inhibitory junction potentials. Ablation of Entpd2 increased gut permeability following inflammation. In conclusion, the location- and context-dependent extracellular nucleotide phosphohydrolysis by NTPDase1 and -2 substantially impacts gut function in health and disease. NEW & NOTEWORTHY Purines are important mediators of gastrointestinal physiology and pathophysiology. Nucleoside triphosphate diphosphohydrolases (NTPDases) regulate extracellular purines, but the roles of specific NTPDases in gut functions are poorly understood. Here, we used Entpd1- and Entpd2-deficient mice to show that the differential and cell-selective regulation of purine hydrolysis by NTPDase1 and -2 plays important roles in barrier function, gut motility, and neuromuscular communication in health and disease.

The enteric nervous system as a regulator of intestinal epithelial barrier function in health and disease

2010 ◽  
Vol 4 (5) ◽  
pp. 637-651 ◽  
Author(s):  
Susanne A Snoek ◽  
Marleen I Verstege ◽  
Guy E Boeckxstaens ◽  
René M van den Wijngaard ◽  
Wouter J de Jonge
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Health And Disease

scholarly journals Computational Modeling of Claudin Structure and Function

2020 ◽  
Vol 21 (3) ◽  
pp. 742 ◽  
Author(s):  
Shadi Fuladi ◽  
Ridaka-Wal Jannat ◽  
Le Shen ◽  
Christopher R. Weber ◽  
Fatemeh Khalili-Araghi
Keyword(s):  
Small Molecules ◽  
Tight Junctions ◽  
Barrier Function ◽  
Functional Model ◽  
Structure And Function ◽  
Structural Basis ◽  
Crystallographic Structure ◽  
Epithelial Barrier Function ◽  
Transport Of Ions ◽  
And Function

Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels.

Increased iNOS activity is essential for pulmonary epithelial tight junction dysfunction in endotoxemic mice

2004 ◽  
Vol 286 (2) ◽  
pp. L259-L267 ◽  
Author(s):  
Xiaonan Han ◽  
Mitchell P. Fink ◽  
Takashi Uchiyama ◽  
Runkuan Yang ◽  
Russell L. Delude
Keyword(s):  
Protein Expression ◽  
Tight Junction ◽  
Barrier Function ◽  
Lavage Fluid ◽  
Tissue Expression ◽  
No Production ◽  
Pulmonary Epithelium ◽  
Epithelial Barrier Function ◽  
Key Factor ◽  
And Function

A murine endotoxemia model and cultured Calu-3 monolayers were used to test the hypothesis that excessive nitric oxide (NO) production secondary to induction of inducible NO synthase (iNOS) is a key factor leading to altered tight junction (TJ) protein expression and function in the pulmonary epithelium. C57Bl/6J mice were injected with either Escherichia coli 0111:B4 lipopolysaccharide (LPS; 2 mg/kg) or vehicle. Twelve hours later, leakage of FITC-dextran ( Mr 4 kDa; FD4) from blood into bronchoalveolar lavage fluid was significantly increased in endotoxemic but not control mice. This decrease in bronchoalveolar barrier function was associated with upregulation of iNOS protein expression and NF-κB activation in lung tissue. Expression of the TJ proteins, zonula occludens (ZO)-1, ZO-2, ZO-3, and occludin, as assessed by immunoblotting and/or immunofluorescence, decreased in lung after the injection of mice with LPS. Treatment of endotoxemic mice with an isoform-selective iNOS inhibitor [l- N6-(1-iminoethyl)lysine; l-NIL] ameliorated LPS-induced changes in TJ protein expression and preserved bronchoalveolar epithelial barrier function. Incubating Calu-3 bronchiolar epithelial monolayers with cytomix (a mixture of 1,000 U/ml IFN-γ, 10 ng/ml TNF-α, and 1 ng/ml IL-1β) increased permeability to FD4, but adding l-NIL prevented this effect. These results suggest that decreased expression and mistargeting of TJ proteins in lung after systemic inflammation may be NO dependent.

scholarly journals Molecular mechanisms of somatostatin-mediated intestinal epithelial barrier function restoration by upregulating claudin-4 in mice with DSS-induced colitis

2018 ◽  
Vol 315 (4) ◽  
pp. C527-C536 ◽  
Author(s):  
Lin Cai ◽  
Xiao Li ◽  
Chong Geng ◽  
Xuelian Lei ◽  
Chunhui Wang
Keyword(s):  
Barrier Function ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Regulatory Elements ◽  
Barrier Structure ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Treatment Regimens ◽  
Tnf Α ◽  
And Function

Intestinal barrier dysfunction plays a crucial role in the pathogenesis of ulcerative colitis (UC). Previous studies have shown somatostatin (SST) can protect intestinal barrier structure possibly through upregulating tight junction (TJ) protein expression, but the mechanisms of this upregulation remain undefined. This study aimed to investigate the molecular mechanisms of interaction of SST with its downstream regulatory elements in DSS-induced colitis mice. In DSS-induced colitis mice, exogenous SST supplement (octreotide) effectively ameliorated disease progression, restored colonic barrier structure and function, and stimulated claudin-4 expression. Similar effects were also observed for SST on Caco-2 cells intervened by TNF-α. SST receptor 5 (SSTR5) agonist L-817,818 upregulated the claudin-4 expression whereas the SSTR2 agonist seglitide could not reverse TNF-α-induced reduction of claudin-4. SST treatment significantly decreased the phosphorylation levels of ERK1/2 and p38 induced by TNF-α. PD-98059 (ERK1/2 pathway inhibitor) but not SB-202190 (p38 pathway inhibitor) could reverse TNF-α-induced suppression of claudin-4 expression. Both inhibitors could improve the TJ barrier function damaged by TNF-α. Our studies suggest that the protective effect of SST on intestinal barrier achieved by upregulating claudin-4 expression through activation of SSTR5 and suppression of the ERK1/2 pathways. These findings will benefit the development of novel treatment regimens for UC.

scholarly journals The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease

2018 ◽  
Vol 19 (9) ◽  
pp. 2560 ◽  
Author(s):  
Abdullah Hoter ◽  
Marwan El-Sabban ◽  
Hassan Naim
Keyword(s):  
Potential Role ◽  
General Structure ◽  
Cell Cycle Control ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Regulation Function ◽  
Health And Disease ◽  
Structure Regulation ◽  
And Function ◽  
Cellular Compartments

The mammalian HSP90 family of proteins is a cluster of highly conserved molecules that are involved in myriad cellular processes. Their distribution in various cellular compartments underlines their essential roles in cellular homeostasis. HSP90 and its co-chaperones orchestrate crucial physiological processes such as cell survival, cell cycle control, hormone signaling, and apoptosis. Conversely, HSP90, and its secreted forms, contribute to the development and progress of serious pathologies, including cancer and neurodegenerative diseases. Therefore, targeting HSP90 is an attractive strategy for the treatment of neoplasms and other diseases. This manuscript will review the general structure, regulation and function of HSP90 family and their potential role in pathophysiology.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

“Because every recipient is also a potential patient” – TV Health Programmes in the FRG and the GDR, from the 1960s to the 1980s

Gesnerus ◽  
2019 ◽  
Vol 76 (2) ◽  
pp. 172-191
Author(s):  
Susanne Vollberg
Keyword(s):  
Public Awareness ◽  
West Germany ◽  
Continuous Coverage ◽  
Public Consciousness ◽  
Television Programme ◽  
East German ◽  
Health And Disease ◽  
Media Systems ◽  
The 1960S ◽  
And Function

In the television programme of West Germany from the 1960s to the 1980s, health magazines like Gesundheitsmagazin Praxis [Practice Health Magazine] (produced by ZDF)1 or ARD-Ratgeber: Gesundheit [ARD Health Advisor] played an important role in addressing health and disease as topics of public awareness. With their health magazine Visite [Doctor’s rounds], East German television, too relied on continuous coverage and reporting in the field. On the example of above magazines, this paper will examine the history, design and function of health communication in magazine-type formats. Before the background of the changes in media policy experienced over three decades and the different media systems in the then two Germanys, it will discuss the question of whether television was able to move health relevant topics and issues into public consciousness.

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