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Carbamylation

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https://www.readbyqxmd.com/read/28183721/carbamylation-of-vimentin-is-inducible-by-smoking-and-represents-an-independent-autoantigen-in-rheumatoid-arthritis
#1
Caroline Ospelt, Holger Bang, Eugen Feist, Giovanni Camici, Stephan Keller, Jacqueline Detert, Anette Krämer, Steffen Gay, Khetam Ghannam, Gerd R Burmester
OBJECTIVES: Smoking has been connected to citrullination of antigens and formation of anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Since smoking can modify proteins by carbamylation (formation of homocitrulline), this study was conducted to investigate these effects on vimentin in animal models and RA. METHODS: The efficiency of enzymatic carbamylation of vimentin was characterised. B-cell response was investigated after immunisation of rabbits with different vimentin isoforms...
February 9, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28149015/role-of-bioflavonoid-quercetin-on-expression-of-urea-cycle-enzymes-astrocytic-and-inflammatory-markers-in-hyperammonemic-rats
#2
Sivamani Kanimozhi, Perumal Subramanian, Sakkaravarthy Shanmugapriya, Subramanian Sathishkumar
This study evaluates the role of quercetin on the expression of urea cycle enzymes, astrocytic, neuronal and inflammatory markers in hyperammonemic rats. Hyperammonemia (provoked by intraperitonial injections of (ammonium chloride-100 mg/kg b.w for 56 days), showed diminished expression of urea cycle enzymes [carbamyl phosphate synthetase-1 (CPS-1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS) and arginase (ARG)] in liver and decreased expression of neuronal and astrocytic markers-glutamine synthase (GS) and phosphate activated glutaminase (PAG) in brain and increased expression of brain inflammatory markers such as interleukin 6 (IL6), inducible nitric oxide synthase (iNOS) and nuclear transcription factor kappa B (NF-κB) (by western blot analysis) and exhibited downregulated expression of soluble guanylate cyclase (sGC), glial fibrillary acidic protein (GFAP) in brain and ASS in liver investigated (by RT-PCR)...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28137483/differential-effect-of-erythropoietin-and-carbamylated-erythropoietin-on-endothelial-cell-migration
#3
Romina E Maltaneri, María E Chamorro, Agustina Schiappacasse, Alcira B Nesse, Daniela C Vittori
No abstract text is available yet for this article.
January 28, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28069651/inhibition-by-avibactam-and-clavulanate-of-the-%C3%AE-lactamases-kpc-2-and-ctx-m-15-harboring-the-substitution-n132g-in-the-conserved-motif-sdn
#4
Clément Ourghanlian, Daria Soroka, Michel Arthur
The substitution N(132)G in the motif SDN of class A β-lactamases from rapidly-growing mycobacteria was previously shown to impair their inhibition by avibactam but to improve the stability of acyl-enzymes formed with clavulanate. The same substitution was introduced in KPC-2 and CTX-M-15 to assess its impact on β-lactamases from Enterobacteriaceae and evaluate whether it could lead to resistance to the ceftazidime-avibactam combination. Kinetic parameters for the inhibition of the β-lactamases by avibactam and clavulanate were determined by spectrophotometry using nitrocefin as the substrate...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28067524/urea-artifacts-interfere-with-immuno-purification-of-lysine-acetylation
#5
Ana Martinez-Val, Fernando Garcia, Pilar Ximénez-Embún, Ailyn Martínez Teresa-Calleja, Nuria Ibarz, Isabel Ruppen, Javier Munoz
Comprehensive analysis of post-translational modifications (PTMs) often depends on the purification of modified peptides prior to LC-MS/MS. The implementation of these enrichment methods requires thorough knowledge of the experimental conditions to achieve optimal selectivity and sensitivity. In this regard, large-scale analysis of lysine acetylation, a key PTM for multiple cellular processes, makes use of monoclonal pan-antibodies designed against this moiety. We report that the immuno-purification of lysine-acetylated peptides is hampered by the copurification of lysine carbamylated peptides, a frequent urea artifact...
January 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28052815/how-do-macrophages-sense-modified-low-density-lipoproteins
#6
REVIEW
Dimitry A Chistiakov, Alexandra A Melnichenko, Alexander N Orekhov, Yuri V Bobryshev
In atherosclerosis, serum lipoproteins undergo various chemical modifications that impair their normal function. Modification of low density lipoprotein (LDL) such as oxidation, glycation, carbamylation, glucooxidation, etc. makes LDL particles more proatherogenic. Macrophages are responsible for clearance of modified LDL to prevent cytotoxicity, tissue injury, inflammation, and metabolic disturbances. They develop an advanced sensing arsenal composed of various pattern recognition receptors (PRRs) capable of recognizing and binding foreign or altered-self targets for further inactivation and degradation...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28039278/inhibition-of-%C3%AE-lactamases-of-mycobacteria-by-avibactam-and-clavulanate
#7
Daria Soroka, Clément Ourghanlian, Fabrice Compain, Marion Fichini, Vincent Dubée, Jean-Luc Mainardi, Jean-Emmanuel Hugonnet, Michel Arthur
OBJECTIVES: Mycobacterium tuberculosis and Mycobacterium abscessus produce broad-spectrum class A β-lactamases, BlaC and BlaMab, which are inhibited by clavulanate and avibactam, respectively. BlaC differs from BlaMab at Ambler position 132 in the conserved motif SDN (SDG versus SDN, respectively). Here, we investigated whether this polymorphism could account for the inhibition specificity of β-lactamases from slowly and rapidly growing mycobacteria. METHODS: Enzyme kinetics were determined to assess the impact of the substitutions G(132)N in BlaC and N(132)G in BlaMab on β-lactamase inhibition by clavulanate and avibactam...
December 30, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28007335/precision-medicine-in-rare-disease-mechanisms-of-disparate-effects-of-n-carbamyl-l-glutamate-on-mutant-cps1-enzymes
#8
Dashuang Shi, Gengxiang Zhao, Nicholas Ah Mew, Mendel Tuchman
This study documents the disparate therapeutic effect of N-carbamyl-l-glutamate (NCG) in the activation of two different disease-causing mutants of carbamyl phosphate synthetase 1 (CPS1). We investigated the effects of NCG on purified recombinant wild-type (WT) mouse CPS1 and its human corresponding E1034G (increased ureagenesis on NCG) and M792I (decreased ureagenesis on NCG) mutants. NCG activates WT CPS1 sub-optimally compared to NAG. Similar to NAG, NCG, in combination with MgATP, stabilizes the enzyme, but competes with NAG binding to the enzyme...
December 8, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27990564/planarian-cholinesterase-in-vitro-characterization-of-an-evolutionarily-ancient-enzyme-to-study-organophosphorus-pesticide-toxicity-and-reactivation
#9
Danielle Hagstrom, Hideto Hirokawa, Limin Zhang, Zoran Radic, Palmer Taylor, Eva-Maria S Collins
The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D...
December 18, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27986757/cyanate-impaired-angiogenesis-association-with-poor-coronary-collateral-growth-in-patients-with-stable-angina-and-chronic-total-occlusion
#10
Jia Teng Sun, Ke Yang, Jing Yan Mao, Wei Feng Shen, Lin Lu, Qi Hong Wu, Yan Ping Wang, Li Ping Wu, Rui Yan Zhang
BACKGROUND: Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. METHODS AND RESULTS: In this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind-limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate-treated mice. Likewise, there were fewer capillaries in the ischemic hind-limb tissue of cyanate-exposed mice...
December 16, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27986080/erratum-to-prevalence-sensitivity-and-specificity-of-antibodies-against-carbamylated-proteins-in-a-monocentric-cohort-of-patients-with-rheumatoid-arthritis-and-other-autoimmune-rheumatic-diseases
#11
Arbi Pecani, Cristiano Alessandri, Francesca Romana Spinelli, Roberta Priori, Valeria Riccieri, Manuela Di Franco, Fulvia Ceccarelli, Tania Colasanti, Monica Pendolino, Riccardo Mancini, Simona Truglia, Cristiana Barbati, Marta Vomero, Danilo Sabatinelli, Francesca Morello, Guido Valesini, Fabrizio Conti
Anti-CarP antibodies were detected in 117 patients with RA (37.9%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sjögren syndrome were positive for anti-CarP...
December 16, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27973558/carbamylated-low-density-lipoprotein-cldl-mediated-induction-of-autophagy-and-its-role-in-endothelial-cell-injury
#12
Chhanda Bose, Sudhir V Shah, Oleg K Karaduta, Gur P Kaushal
Patients with chronic kidney disease (CKD) have high risk of cardiovascular complications. Plasma levels of carbamylated proteins produced by urea-derived isocyanate or thiocyanate are elevated in CKD patients and that they are significant predictors of cardiovascular events and all-cause mortality. Carbamylated LDL (cLDL) has pro-atherogenic properties and is known to affect major biological processes relevant to atherosclerosis including endothelial cell injury. The underlying mechanisms of cLDL-induced endothelial cell injury are not well understood...
2016: PloS One
https://www.readbyqxmd.com/read/27926664/short-article-absence-of-serological-rheumatoid-arthritis-biomarkers-in-inflammatory-bowel-disease-patients-with-arthropathies
#13
Sanne J H Van Erp, Marije K Verheul, E W Nivine Levarht, Johan J van der Reijden, Désirée van der Heijde, Floris A van Gaalen, Daniel W Hommes, Gary L Norman, Zakera Shums, Michael Mahler, Hein W Verspaget, Leendert A Trouw, Andrea E van der Meulen-de Jong
OBJECTIVE: Biomarkers that are associated with future progression to rheumatoid arthritis (RA) and joint destruction have been discovered previously in patients with arthralgia. The present study examined these RA biomarkers in inflammatory bowel disease (IBD) patients with arthropathies. PATIENTS AND METHODS: Sera from 155 IBD patients with and 99 IBD patients without arthropathies were analyzed for immunoglobulin (Ig) M rheumatoid factor (RF), IgA-RF, anti-cyclic citrullinated peptide 2, anti-cyclic citrullinated peptide 3...
March 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27912793/antibodies-against-carbamylated-proteins-and-cyclic-citrullinated-peptides-in-systemic-lupus-erythematosus-results-from-two-well-defined-european-cohorts
#14
Michael Ziegelasch, Myrthe A M van Delft, Philip Wallin, Thomas Skogh, César Magro-Checa, Gerda M Steup-Beekman, Leendert A Trouw, Alf Kastbom, Christopher Sjöwall
BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27906045/smoking-is-associated-with-the-concurrent-presence-of-multiple-autoantibodies-in-rheumatoid-arthritis-rather-than-with-anti-citrullinated-protein-antibodies-per-se-a-multicenter-cohort-study
#15
Tineke J van Wesemael, Sofia Ajeganova, Jennifer Humphreys, Chikashi Terao, Ammar Muhammad, Deborah P M Symmons, Alex J MacGregor, Ingiäld Hafström, Leendert A Trouw, Annette H M van der Helm-van Mil, Tom W J Huizinga, Tsuneyo Mimori, René E M Toes, Fumihiko Matsuda, Björn Svensson, Suzanne M M Verstappen, Diane van der Woude
BACKGROUND: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27887639/prevalence-sensitivity-and-specificity-of-antibodies-against-carbamylated-proteins-in-a-monocentric-cohort-of-patients-with-rheumatoid-arthritis-and-other-autoimmune-rheumatic-diseases
#16
Arbi Pecani, Cristiano Alessandri, Francesca Romana Spinelli, Roberta Priori, Valeria Riccieri, Manuela Di Franco, Fulvia Ceccarelli, Tania Colasanti, Monica Pendolino, Riccardo Mancini, Simona Truglia, Cristiana Barbati, Marta Vomero, Danilo Sabatinelli, Francesca Morello, Guido Valesini, Fabrizio Conti
BACKGROUND: Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs). METHODS: Serum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated...
November 25, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27872172/urea-a-true-uremic-toxin-the-empire-strikes-back
#17
REVIEW
Wei Ling Lau, Nosratola D Vaziri
Blood levels of urea rise with progressive decline in kidney function. Older studies examining acute urea infusion suggested that urea was well-tolerated at levels 8-10× above normal values. More recent in vitro and in vivo work argue the opposite and demonstrate both direct and indirect toxicities of urea, which probably promote the premature aging phenotype that is pervasive in chronic kidney disease (CKD). Elevated urea at concentrations typically encountered in uremic patients induces disintegration of the gut epithelial barrier, leading to translocation of bacterial toxins into the bloodstream and systemic inflammation...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27809929/insight-of-brain-degenerative-protein-modifications-in-the-pathology-of-neurodegeneration-and-dementia-by-proteomic-profiling
#18
REVIEW
Sunil S Adav, Siu Kwan Sze
Dementia is a syndrome associated with a wide range of clinical features including progressive cognitive decline and patient inability to self-care. Due to rapidly increasing prevalence in aging society, dementia now confers a major economic, social, and healthcare burden throughout the world, and has therefore been identified as a public health priority by the World Health Organization. Previous studies have established dementia as a 'proteinopathy' caused by detrimental changes in brain protein structure and function that promote misfolding, aggregation, and deposition as insoluble amyloid plaques...
November 3, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27777975/the-role-for-neutrophil-extracellular-traps-in-cystic-fibrosis-autoimmunity
#19
Sladjana Skopelja, B JoNell Hamilton, Jonathan D Jones, Mei-Ling Yang, Mark Mamula, Alix Ashare, Alex H Gifford, William F C Rigby
While respiratory failure in cystic fibrosis (CF) frequently associates with chronic infection by Pseudomonas aeruginosa, no single factor predicts the extent of lung damage in CF. To elucidate other causes, we studied the autoantibody profile in CF and rheumatoid arthritis (RA) patients, given the similar association of airway inflammation and autoimmunity in RA. Even though we observed that bactericidal permeability-increasing protein (BPI), carbamylated proteins, and citrullinated proteins all localized to the neutrophil extracellular traps (NETs), which are implicated in the development of autoimmunity, our study demonstrates striking autoantibody specificity in CF...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27773721/identification-of-krt16-as-a-target-of-an-autoantibody-response-in-complex-regional-pain-syndrome
#20
Maral Tajerian, Victor Hung, Hamda Khan, Lauren J Lahey, Yuan Sun, Frank Birklein, Heidrun H Krämer, William H Robinson, Wade S Kingery, J David Clark
OBJECTIVE: Using a mouse model of complex regional pain syndrome (CRPS), our goal was to identify autoantigens in the skin of the affected limb. METHODS: A CRPS-like state was induced using the tibia fracture/cast immobilization model. Three weeks after fracture, hindpaw skin was homogenized, run on 2-d gels, and probed by sera from fracture and control mice. Spots of interest were analyzed by liquid chromatography-mass spectroscopy (LC-MS) and the list of targets validated by examining their abundance and subcellular localization...
January 2017: Experimental Neurology
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