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Transglutaminase 2

Éva Sivadó, Sabrina Lareure, Valérie Attuil-Audenis, Saïd El Alaoui, Vincent Thomas
Tissue transglutaminase (tTG) belongs to the multigene transglutaminase family of Ca(2+)-dependent protein cross-linking enzymes. There is a strong evidence that tTG is involved in pathology, such as neurodegenerative diseases, cancer, and celiac disease. To study physiopathological implication of tTG, a sandwich immunoassay has been developed with a new monoclonal antibody for the capture and polyclonal antibody both generated in house. Using this ready to use assay, the tTG protein level can be measured in human tissue homogenates and cells extracts easily in about 4 h...
October 19, 2016: Amino Acids
Carmine Carbone, Elena Di Gennaro, Geny Piro, Maria Rita Milone, Biagio Pucci, Michele Caraglia, Alfredo Budillon
Vorinostat demonstrated preclinical and clinical efficacy in human cancers and is the first histone deacetylase inhibitor (HDACi) approved for cancer treatment. Tissue transglutaminase (TG2) is a multifunctional enzyme that catalyzes a Ca(2+) dependent transamidating reaction resulting in covalent cross-links between proteins. TG2 acts also as G-protein in trans-membrane signaling and as a cell surface adhesion mediator. TG2 up-regulation has been demonstrated in several cancers and its expression levels correlate with resistance to chemotherapy and metastatic potential...
October 19, 2016: Amino Acids
Prasenjit Das, Ramakant Rawat, Anil K Verma, Geetika Singh, Archana G Vallonthaiel, Rajni Yadav, Gaurav P S Gahlot, Amit K Dinda, Vineet Ahuja, Siddhartha Datta Gupta, Sanjay K Agarwal, Govind K Makharia
Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Andrew J Irvine, William D Chey, Alexander C Ford
OBJECTIVES: Celiac disease (CD) and irritable bowel syndrome (IBS) share similar symptoms, leading to confusion between the two and diagnostic delay. International guidelines recommend screening individuals with IBS for CD, via serological testing. However, studies published recently have cast doubt on the utility of this. We updated a previous meta-analysis examining this issue. METHODS: MEDLINE, EMBASE, and EMBASE Classic were searched through to May 2016. Eligible studies recruited adults with IBS according to symptom-based criteria, physician's opinion, or questionnaire data...
October 18, 2016: American Journal of Gastroenterology
Ding-Jun Hao, Cuicui Liu, Lingling Zhang, Bo Chen, Qian Zhang, Rui Zhang, Jing An, Jingjing Zhao, Mingmei Wu, Yi Wang, Alfred Simental, Baorong He, Hao Yang
The gradual deterioration following central nervous system (CNS) injuries or neurodegenerative disorders is usually accompanied by infiltration of degenerated and apoptotic neural tissue debris. A rapid and efficient clearance of these deteriorated cell products is of pivotal importance in creating a permissive environment for regeneration of those damaged neurons. Our recent report revealed that the phagocytic activity of olfactory ensheathing cells (OECs) can make a substantial contribution to neuronal growth in such a hostile environment...
October 14, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
E Kamycheva, T Goto, C A Camargo
: We investigated the association between celiac disease (CD) and bone mass density (BMD) and risk of osteoporotic fractures in the general US population. In children and men ≥18 years, CD was associated with reduced BMD, and in men ≥40 years, CD was associated with increased risk of osteoporotic fractures. INTRODUCTION: Celiac disease (CD) is an autoimmune condition, characterized by inflammation of the small intestine. CD has an increasing prevalence, and if unrecognized or untreated, CD can lead to complications from malabsorption and micronutrient deficiencies...
October 6, 2016: Osteoporosis International
Nancy A McNamara, Shaokui Ge, Salena M Lee, Alison M Enghauser, Lindsey Kuehl, Feeling Y-T Chen, Marianne Gallup, Robert L McKown
Purpose: To determine whether levels of endogenous tear protein, lacritin, are linked to altered corneal innervation and dry eye severity in patients with Sjögren's syndrome (SS). Methods: Clinical data were obtained from 10 SS and 10 age-matched controls. Enzyme-linked immunosorbent assay was used to assess total tear lacritin extracted from Schirmer strips. Western blot was used to detect active lacritin monomer (∼25 kDa), active lacritin fragment (∼12-15 kDa), and inactive tissue transglutaminase-generated lacritin (≥40 kDa)...
October 1, 2016: Investigative Ophthalmology & Visual Science
Izhar Burhan, Giulia Furini, Hugues Lortat-Jacob, Adeola G Atobatele, Alessandra Scarpellini, Nina Schroeder, John Atkinson, Mabrouka Maamra, Faith H Nutter, Philip Watson, Manlio Vinciguerra, Timothy S Johnson, Elisabetta A M Verderio
Transglutaminase-2 (TG2) is a new anti-fibrotic target for chronic kidney disease, for its role in altering the extracellular homeostatic balance leading to excessive build-up of matrix in kidney. However, there is no confirmation that TG2 is the only transglutaminase involved, neither there are strategies to control its action specifically over that of the conserved family-members. In this study, we have profiled transglutaminase isozymes in the rat subtotal nephrectomy (SNx) model of progressive renal scarring...
October 3, 2016: Scientific Reports
Courtney E Hart, Michael J Lauth, Cassidy S Hunter, Brennan R Krasny, Kristin M Hardy
The xenoestrogen 4-nonylphenol (NP) is a ubiquitous aquatic pollutant and has been shown to impair reproduction, development, growth and, more recently, immune function in marine invertebrates. We investigated the effects of short-term (7 d) exposure to low (2 μg l(-1)) and high (100 μg l(-1)) levels of NP on cellular and humoral elements of the innate immune response of Crassostrea gigas to a bacterial challenge. To this end, we measured 1) total hemocyte counts (THC), 2) relative transcript abundance of ten immune-related genes (defh1, defh2, bigdef1, bigdef2, bpi, lysozyme-1, galectin, C-type lectin 2, timp, and transglutaminase) in the hemocytes, gill and mantle, and 3) hemolymph plasma lysozyme activity, following experimental Vibrio campbellii infection...
September 28, 2016: Fish & Shellfish Immunology
Jorunn Stamnaes, Inês Cardoso, Rasmus Iversen, Ludvig M Sollid
Transglutaminase 2 (TG2) is a ubiquitous crosslinking enzyme present in both intra- and extracellular in many cell types and tissues. TG2 is upregulated upon cellular stress or injury, and extracellular TG2 is implicated in several human diseases, including celiac disease. However, incomplete knowledge about extracellular TG2 biology limits our understanding of how TG2 is involved in disease. Here, we demonstrate that binding of TG2 to the ECM of small intestinal tissue sections is the sum of binding to fibronectin (FN) via its N-terminal domain and binding to an abundant, novel extracellular matrix (ECM) interaction partner via its second C-terminal beta-barrel domain...
September 29, 2016: FEBS Journal
Helen Troilo, Ruth Steer, Richard F Collins, Cay M Kielty, Clair Baldock
TGFβ plays key roles in fibrosis and cancer progression, and latency is conferred by covalent linkage to latent TGFβ binding proteins (LTBPs). LTBP1 is essential for TGFβ folding, secretion, matrix localization and activation but little is known about its structure due to its inherent size and flexibility. Here we show that LTBP1 adopts an extended conformation with stable matrix-binding N-terminus, extended central array of 11 calcium-binding EGF domains and flexible TGFβ-binding C-terminus. Moreover we demonstrate that LTBP1 forms short filament-like structures independent of other matrix components...
September 28, 2016: Scientific Reports
Giuseppe Losurdo, Floriana Giorgio, Domenico Piscitelli, Lucia Montenegro, Claudia Covelli, Maria Grazia Fiore, Antonio Giangaspero, Andrea Iannone, Mariabeatrice Principi, Annacinzia Amoruso, Michele Barone, Alfredo Di Leo, Enzo Ierardi
AIM: To evaluate mucosal baseline mRNA expression of tissue transglutaminase 2 (tTG2), interferon gamma (IFNγ), toll-like receptor 2 (TLR2) and Myeloid Differentiation factor 88 (MyD88) in patients with microscopic enteritis (ME). METHODS: We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count (IELs)...
September 21, 2016: World Journal of Gastroenterology: WJG
Ji Zhang, Yi-Rong Ding, Rui Wang
AIM: Tissue transglutaminase (tTG) catalyzes proteins, including β-amyloid (Aβ), to cross-link as a γ-glutamyl-ε-lysine structure isopeptide, which is highly resistant to proteolysis. Thus, tTG plays an important role in protein accumulation in Alzheimer's disease (AD). In the present study, we examined the effect of an irreversible tTG inhibitor, NTU283, on Aβ mimic-induced AD pathogenesis in SH-SY5Y cells. METHODS: Western blot and in-cell Western analyses were used to detect tTG and isopeptide (representing the enzyme activity of tTG) protein levels...
September 26, 2016: Acta Pharmacologica Sinica
Yutaka Furutani, Mariko Toguchi, Rajan Shrestha, Soichi Kojima
Transglutaminase 2 (TG2) localizes to the nucleus and induces apoptosis through a crosslinking inactivation of Sp1 in JHH-7 cells treated with acyclic retinoid. We screened an inhibitor suppressing transamidase activity in the nucleus without affecting transamidase activity itself. Phenosafranin was found to inhibit nuclear localization of EGFP-tagged TG2 and dose-dependently reduce nuclear transamidase activity without affecting the activity in a tube. We concluded that phenosafranin was a novel TG2 inhibitor capable of suppressing its nuclear localization...
September 24, 2016: Amino Acids
Anshu Srivastava, Saurabh Chaturvedi, Preeti Dabadghao, Amrita Mathias, Umesh Shukla, Uttam Singh, Surender Kumar Yachha
BACKGROUND: Type 1 diabetes (T1D) patients are at an increased risk of having celiac disease (CD). We evaluated the prevalence and clinical profile of CD in children and adolescents with T1D and reviewed the Indian literature to determine prevalence and reasons for variability. METHODS: In this cross-sectional study, subjects with T1D were prospectively evaluated with a demographic and gastrointestinal (GI) questionnaire, human IgA-tissue transglutaminase (IgA-tTGA), and endoscopic duodenal biopsy in serology positive patients...
September 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Tiziana Russo, Monica Currò, Anna Barbera, Daniela Caccamo, Pietro Antonuccio, Salvatore Arena, Angela Simona Montalto, Saveria Parisi, Lucia Marseglia, Eloisa Gitto, Riccardo Ientile, Pietro Impellizzeri, Carmelo Romeo
Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder of unclear etiology. The etiology and the exact molecular mechanisms underlying the disease are still unknown. The human transglutaminase (TG) family consists of several proteins with catalytic activity essential for biological processes. In the present research we investigated the transcript levels of three TGs in patients operated on for congenital phimosis without or with histologically confirmed BXO; Thirty children with acquired phimosis were enrolled...
2016: International Journal of Molecular Sciences
Vanesa Soledad Marin Viegas, Carolina Gabriela Ocampo, Silvana Petruccelli
Delivery of recombinant proteins to vegetative tissue vacuoles was considered inconvenient since this compartment was expected to be hydrolytic; nevertheless there is growing evidence that certain foreign proteins accumulate at high yields in vacuoles. For example avidin, cellulolytic enzymes, endolysin, and transglutaminases were produced at high yields when were sorted to leaf central vacuole avoiding the detrimental effect of these proteins on plant growth. Also, several secretory mammalian proteins such as collagen, α1-proteinase inhibitor, complement-5a, interleukin-6 and immunoglobulins accumulated at higher yields in leaf vacuoles than in the apoplast or cytosol...
September 20, 2016: Bioengineered
T Matthias, P Jeremias, S Neidhöfer, A Lerner
Microbial transglutaminase (mTg) is capable of cross-linking numerous molecules. It is a family member of human tissue transglutaminase (tTg), and is involved in CD. Despite declarations of the safety of mTg for industrial use, direct evidence for immunogenicity of the enzyme is lacking. The serological activity of mTg, tTg, gliadin complexed mTg (mTg neo-epitope) and gliadin complexed tTg (tTg neo-epitope) were studied in 95 pediatric celiac patients (CD), 99 normal children (NC), 79 normal adults (NA) and 45 children with nonspecific abdominal pain (AP)...
September 15, 2016: Autoimmunity Reviews
Martina Cordella, Claudio Tabolacci, Stefania Rossi, Cinzia Senatore, Angelo M Facchiano, Daniela D'Arcangelo, Antonio Facchiano, Francesco Facchiano
Migration is a key cellular function with important implications in cell physiology. Impairment of such function is observed in angiogenesis, cancer, central nervous system development, and many other physiological and pathological events. Serum is considered among the most potent physiological chemotactic stimuli. Transglutaminase 2 (TG2) is involved in most of the mentioned processes, suggesting the hypothesis that TG2 may modulate cell movement and chemotaxis by acting on serum factors. Cell biology and biochemistry studies confirmed this hypothesis, showing that human serum contains potent chemotactic signals significantly impaired by activated TG2...
September 16, 2016: Amino Acids
Michelle Shui Yee Lau, Peter Mooney, William White, Victoria Appleby, Sulleman Moreea, Ismail Haythem, Joshua Elias, Kiran Bundhoo, Gareth Corbett, Liam Wong, Her Hsin Tsai, Simon Cross, John Hebden, Sami Hoque, David Sanders
BACKGROUND: International guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance...
September 15, 2016: BMC Gastroenterology
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