A5001935220- Barrier Structure and Function Studies
- Alcohol Consumption and Health Effects
- Connexins and lens biology
- Gut microbiota and health
- Liver Disease Diagnosis and Treatment
- Helicobacter pylori-related gastroenterology studies
- Advanced Fluorescence Microscopy Techniques
- Diet and metabolism studies
- Neurological Disease Mechanisms and Treatments
- Digestive system and related health
- Biochemical Analysis and Sensing Techniques
- Spectroscopy Techniques in Biomedical and Chemical Research
- Cancer Cells and Metastasis
- Growth Hormone and Insulin-like Growth Factors
- Optical Imaging and Spectroscopy Techniques
- Tryptophan and brain disorders
- Effects of Radiation Exposure
- Fatty Acid Research and Health
- Photoreceptor and optogenetics research
- Metabolomics and Mass Spectrometry Studies
- Dietary Effects on Health
- Photoacoustic and Ultrasonic Imaging
- Liver Disease and Transplantation
- Birth, Development, and Health
- Gastrointestinal motility and disorders
University of Tennessee Health Science Center
2015-2024
Memphis VA Medical Center
2021-2023
Janssen (United States)
2022
Veterans Health Administration
2021
Czech Academy of Sciences, Institute of Physiology
2008
University Hospital of Wales
2007
University of Memphis
2007
Indian Institute of Science Bangalore
2001-2004
University of Tennessee at Knoxville
2002-2003
Medical University of South Carolina
1995-2001
The oxidative-stress-induced alteration in paracellular junctional complexes was analysed Caco-2 cell monolayer. Oxidative stress induced a rapid increase tyrosine phosphorylation of occludin, zonula occludens (ZO)-1, E-cadherin and beta-catenin. An decrease transepithelial electrical resistance associated with redistribution occludin-ZO-1 E-cadherin-beta-catenin from the intercellular junctions. Genistein, kinase inhibitor, prevented protein complexes. Occludin, ZO-1, beta-catenin...
Mounting body of evidence indicates that the disruption epithelial tight junctions and resulting loss barrier function play a crucial role in pathogenesis variety gastrointestinal, hepatic, pulmonary, kidney ocular diseases. Increased production inflammatory mediators such as cytokines reactive oxygen species disrupt endothelial by destabilizing junctions. Oxidative stress induced various hydrogen peroxide, nitric oxide, peroxynitrite hypochlorous acid tissues. The mechanism involved...
The MAPK (mitogen-activated protein kinase) pathway is a major intracellular signalling involved in EGF (epithelial growth factor) receptor-mediated cell and differentiation. A novel function of activity the mechanism EGF-mediated protection TJs (tight junctions) from H2O2 was examined Caco-2 monolayers. prevention H2O2-induced increase paracellular permeability associated with Tyr-phosphorylation, Thr-dephosphorylation cellular redistribution occludin ZO-1 (zonula occludin-1). also...
PKC eta is expressed predominantly in the epithelial tissues; however, its role regulation of tight junctions (TJs) unknown. We present evidence that phosphorylates occludin on threonine residues (T403 and T404) plays a crucial assembly and/or maintenance TJs Caco-2 MDCK cell monolayers. Inhibition by specific pseudo substrate inhibitor or knockdown shRNA disrupts junctional distribution ZO-1 compromises barrier function. Expression dominant negative, eta(K394R) TJ function, whereas...
Occludin is the first transmembrane protein of tight junction to be discovered. While numerous studies emphasized important role occludin in assembly and maintenance junctions, knockout indicated that it was not required for different epithelia. However, a detailed characterization mouse concluded gene indispensable, plays complex regulation epithelial junctions organs. This article describes phosphorylation its into junctions. highly phosphorylated on Ser Thr residues, while...
Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junction (TJ); however, the role of this phosphorylation assembly TJ unclear. The influence protein phosphatases PP2A PP1 occludin was evaluated Caco-2 cells. Protein phosphatase inhibitors reduced expression PP2A-Calpha PP1alpha accelerated calcium-induced increase transepithelial electrical resistance barrier to inulin permeability also enhanced junctional organization ZO-1 during assembly. Phosphorylation...
The goals of this study were to evaluate the effects ionizing radiation on apical junctions in colonic epithelium and mucosal barrier function mice vivo. Adult subjected total body irradiation (4 Gy) with or without N-acetyl-l-cysteine (NAC) feeding for 5 days before irradiation. At 2-24 h postirradiation, integrity epithelial tight (TJ), adherens (AJ), actin cytoskeleton was assessed by immunofluorescence microscopy immunoblot analysis detergent-insoluble fractions TJ AJ proteins. evaluated...
Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by memory loss and cognitive decline, is major cause of death disability among the older population. Despite decades scientific research, underlying etiological triggers are unknown. Recent studies suggested that gut microbiota can influence AD progression; however, potential mechanisms linking with pathogenesis remain obscure. In present study, we provided mechanistic link between dysbiotic neuroinflammation...
The activity of Src kinases appears to play a role in both assembly and disassembly tight junction. However, the specific isoform kinase regulation junction is not known. In present study c-Src epithelial was investigated Caco-2 cell monolayers. Oxidative stress (xanthine oxidase + xanthine) induced an activation membrane translocation c-Src. oxidative stress-induced decrease transepithelial electrical resistance, increase inulin permeability, redistribution occludin ZO-1 from intercellular...
Acetaldehyde-induced cytotoxicity is an important factor in pathogenesis of alcohol-related diseases; however, the mechanism this toxicity unknown. We recently showed that acetaldehyde increases epithelial paracellular permeability. asked whether protein tyrosine phosphorylation via modulation kinases and/or PTPases a involved acetaldehyde-induced disruption tight junctions Caco-2 cell monolayer. Immunofluorescence localization occludin and ZO-1 acetaldehyde-treated Administration genistein...
The effect of hydrogen peroxide (H 2 O ) on intestinal epithelial barrier function was examined in Caco-2 and T84 cell monolayers. H reduced transepithelial electrical resistance (TER) This decrease TER associated with a dilution potential an increase [ 3 H]mannitol permeability, suggesting -induced disruption the paracellular junctional complexes. administration also induced tyrosine phosphorylation several proteins (at molecular mass ranges 50–90, 100–130, 150–180 kDa) Phenylarsine oxide...
Acetaldehyde, a toxic metabolite of ethanol oxidation, is suggested to play role in the increased risk for gastrointestinal cancers alcoholics. In present study, effect acetaldehyde on tyrosine phosphorylation, immmunofluorescence localization, and detergent-insoluble fractions tight junction adherens proteins was determined human colonic mucosa. The EGF l-glutamine prevention acetaldehyde-induced effects also evaluated. Acetaldehyde reduced protein phosphatase activity, thereby increasing...
Protein kinases play an important role in the regulation of epithelial tight junctions. In present study, we investigated PKCζ (protein kinase Cζ) junction Caco-2 and MDCK (Madin–Darby canine kidney) cell monolayers. Inhibition by a specific pseudosubstrate peptide results redistribution occludin ZO-1 (zona occludens 1) from intercellular junctions disruption barrier function without affecting viability. Reduced expression antisense oligonucleotide or shRNA (short hairpin RNA) also...
Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis mice with symptoms similar to However, mechanism DSS-induced unknown. We investigated disruption and barrier dysfunction Caco-2 cell monolayers vitro mouse colon vivo. DSS treatment resulted junctions, adherens actin cytoskeleton leading monolayers. induced a rapid activation c-Jun N-terminal kinase (JNK), inhibition or knockdown JNK2...
The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated Caco-2 cell monolayers vitro restraint stress-induced barrier dysfunction mouse colon vivo Live imaging showed that stretch DSS triggered rapid production ROS monolayers, which blocked by depletion intracellular Ca2+ 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Knockdown CaV1.3 or TRPV6 channels stress DSS-induced...
Abstract Alcohol use disorders are associated with altered stress responses, but the impact of or hormones on alcohol-associated tissue injury remain unknown. We evaluated effects chronic restraint alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is hormone stress-induced effects, we effect treatment alcoholic at Gut-Liver-Brain (GLB) axis. Chronic synergized epithelial tight junction disruption mucosal mouse intestine. These were...
Intestinal epithelial tight junction disruption is a primary contributing factor in alcohol-associated endotoxemia, systemic inflammation, and multiple organ damage. Ethanol acetaldehyde disrupt junctions by elevating intracellular Ca2+. Here we identify TRPV6, Ca2+-permeable channel, as responsible for alcohol-induced elevation of Ca2+, intestinal barrier dysfunction, inflammation. elicit TRPV6 ionic currents Caco-2 cells. Studies cell monolayers mouse organoids show that deficiency or...
Interactions between E-cadherin, β-catenin and PTP1B (protein tyrosine phosphatase 1B) are crucial for the organization of AJs (adherens junctions) epithelial cell–cell adhesion. In present study, effect acetaldehyde on interactions was determined in Caco-2 cell monolayers. Treatment monolayers with induced redistribution E-cadherin from intercellular junctions by a phosphorylation-dependent mechanism. The PTPase activity associated significantly reduced interaction attenuated acetaldehyde....