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Homocitrullination or carbamylation

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https://www.readbyqxmd.com/read/28545441/association-between-antibodies-to-carbamylated-proteins-and-subclinical-atherosclerosis-in-rheumatoid-arthritis-patients
#1
Francesca Romana Spinelli, Arbi Pecani, Francesco Ciciarello, Tania Colasanti, Manuela Di Franco, Francesca Miranda, Fabrizio Conti, Guido Valesini, Cristiano Alessandri
BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients...
May 25, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28526580/biomarkers-for-rheumatoid-arthritis-from-molecular-processes-to-diagnostic-applications-current-concepts-and-future-perspectives
#2
REVIEW
Britt Nakken, Gábor Papp, Vidar Bosnes, Margit Zeher, György Nagy, Peter Szodoray
Early diagnosis and immediately started appropriate treatment are mandatory for the prevention of radiographic progression, functional disability and unfavourable disease outcome in rheumatoid arthritis (RA). The current classification criteria for RA include two different types of biomarkers representing inflammatory processes, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) or immune processes including autoantibodies, such as rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA)...
May 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28523105/carbamylmethyl-mercaptoacetate-thioether-a-novel-scaffold-for-the-development-of-l1-metallo-%C3%AE-lactamase-inhibitors
#3
Ya-Nan Chang, Yang Xiang, Yue-Juan Zhang, Wen-Ming Wang, Cheng Chen, Peter Oelschlaeger, Ke-Wu Yang
Given the clinical importance of metallo-β-lactamases (MβLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MβLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 μM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 μM and an IC50 value of 0...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28507178/anti-carbamylated-protein-antibodies-are-detectable-in-various-connective-tissue-diseases
#4
Shuichiro Nakabo, Hajime Yoshifuji, Motomu Hashimoto, Yoshitaka Imura, Ran Nakashima, Kosaku Murakami, Nobuo Kuramoto, Shinji Ito, Junko Satoh, Masao Tanaka, Takao Fujii, Tsuneyo Mimori, Koichiro Ohmura
OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are possible diagnostic biomarkers of anticitrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA). We aimed to elucidate the prevalence of anti-CarP antibodies in non-RA connective tissue diseases (CTD) because CTD are important in the differential diagnosis of ACPA-negative RA. METHODS: The sera from 266 patients with RA and 616 patients with CTD and 80 healthy controls were examined using an in-house anti-CarP ELISA...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28483282/a-new-method-to-characterize-the-kinetics-of-cholinesterases-inhibited-by-carbamates
#5
Qiaoling Xiao, Huimin Zhou, Hong Wei, Huaqiao Du, Wen Tan, Yiyi Zhan, Marco Pistolozzi
The inhibition of cholinesterases (ChEs) by carbamates includes a carbamylation (inhibition) step, in which the drug transfers its carbamate moiety to the active site of the enzyme and a decarbamylation (activity recovery) step, in which the carbamyl group is hydrolyzed from the enzyme. The carbamylation and decarbamylation kinetics decide the extent and the duration of the inhibition, thus the full characterization of candidate carbamate inhibitors requires the measurement of the kinetic constants describing both steps...
April 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28451788/the-role-of-autoantibodies-in-the-pathophysiology-of-rheumatoid-arthritis
#6
REVIEW
V F A M Derksen, T W J Huizinga, D van der Woude
Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking...
April 27, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28442530/breach-of-autoreactive-b-cell-tolerance-by-post-translationally-modified-proteins
#7
Jacqueline S Dekkers, Marije K Verheul, Jeroen N Stoop, Bisheng Liu, Andreea Ioan-Facsinay, Peter A van Veelen, Arnoud H de Ru, George M C Janssen, Martin Hegen, Steve Rapecki, Tom W J Huizinga, Leendert A Trouw, René E M Toes
OBJECTIVES: Over 50% of patients with rheumatoid arthritis (RA) harbour a variety of anti-modified protein antibodies (AMPA) against different post-translationally modified (PTM) proteins, including anti-carbamylated protein (anti-CarP) antibodies. At present, it is unknown how AMPA are generated and how autoreactive B cell responses against PTM proteins are induced. Here we studied whether PTM foreign antigens can breach B cell tolerance towards PTM self-proteins. METHODS: Serum reactivity towards five carbamylated proteins was determined for 160 patients with RA and 40 healthy individuals...
April 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28407121/urea-and-chronic-kidney-disease-the-comeback-of-the-century-in-uraemia-research
#8
Raymond Vanholder, Tessa Gryp, Griet Glorieux
Urea, a marker of uraemic retention in chronic kidney disease (CKD) and of adequacy of intradialytic solute removal, has traditionally been considered to be biologically inert. However, a number of recent experimental data suggest that urea is toxic at concentrations representative for CKD. First of all, at least five studies indicate that urea itself induces molecular changes related to insulin resistance, free radical production, apoptosis and disruption of the protective intestinal barrier. Second, urea is at the origin of the generation of cyanate, ammonia and carbamylated compounds, which as such all have been linked to biological changes...
April 12, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28400100/carbamylation-and-oxidation-of-proteins-lead-to-apoptotic-death-of-lymphocytes
#9
Anna Pieniazek, Krzysztof Gwozdzinski
The apoptotic/necrotic changes in isolated human peripheral blood mononuclear cells (MNCs) subjected to hydrogen peroxide (H2O2), cyanate (NaOCN) and their combination were examined. The mitochondrial potential (ΔΨm), the activities of caspases (-2, -3, -6, -8 and -9) and the level of carbonyls and amino groups in proteins were determined and DNA fragmentation. Apoptotic or necrotic cells were identified by fluorescence microscopy using double staining with Hoechst 33258/propidium iodide. Treatment of MNCs with NaOCN (1 mmol/L and 2 mmol/L), alone and in combination with H2O2 (100 μmol/L), led to a significant decrease in the content of amine groups and a significant increase in the carbonyl level of MNCs in comparison with the control...
May 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28398552/carbamylated-albumin-is-one-of-the-target-antigens-of-anti-carbamylated-protein-antibodies
#10
Shuichiro Nakabo, Motomu Hashimoto, Shinji Ito, Moritoshi Furu, Hiromu Ito, Takao Fujii, Hajime Yoshifuji, Yoshitaka Imura, Ran Nakashima, Kosaku Murakami, Nobuo Kuramoto, Masao Tanaka, Junko Satoh, Akihito Ishigami, Satoshi Morita, Tsuneyo Mimori, Koichiro Ohmura
Objectives.: Anti-carbamylated protein (anti-CarP) antibodies are detected in RA patients. Fetal calf serum is used as an antigen source in anti-CarP ELISA, and the precise target antigens have not been found. We aimed to identify the target antigens of anti-CarP antibodies. Methods.: Western blotting of anti-CarP antibodies was conducted. Anti-carbamylated human albumin (CarALB) antibody was detected by in-house ELISA for 493 RA patients and 144 healthy controls (HCs)...
April 7, 2017: Rheumatology
https://www.readbyqxmd.com/read/28386136/assessment-of-anti-carp-antibodies-disease-activity-and-quality-of-life-in-rheumatoid-arthritis-patients-on-conventional-and-biological-disease-modifying-antirheumatic-drugs
#11
Sudhir Kumar, Ghanshyam Pangtey, Rachna Gupta, Harmeet Singh Rehan, Lalit Kumar Gupta
OBJECTIVE: Good biomarkers are important to guide decisions in the clinical management of rheumatoid arthritis (RA). RA patients harbor antibodies directed against carbamylated proteins which may predict joint damage. This study investigated whether antibodies against carbamylated proteins (anti-CarP) may serve as surrogate prognostic markers. MATERIAL AND METHODS: Fifty-three patients with a diagnosis of rheumatoid arthritis according to ACR 1987 criteria were included...
2017: Reumatologia
https://www.readbyqxmd.com/read/28382370/impact-of-fibrinogen-carbamylation-on-fibrin-clot-formation-and-stability
#12
Veronika Binder, Brith Bergum, Stéphane Jaisson, Philippe Gillery, Carsten Scavenius, Endy Spriet, Anne Karin Nyhaug, Helen M Roberts, Iain L C Chapple, Annelie Hellvard, Nicolas Delaleu, Piotr Mydel
Carbamylation is a non-enzymatic post-translational modification induced upon exposure of free amino groups to urea-derived cyanate leading to irreversible changes of protein charge, structure and function. Levels of carbamylated proteins increase significantly in chronic kidney disease and carbamylated albumin is considered as an important biomarker indicating mortality risk. High plasma concentrations and long half-life make fibrinogen a prime target for carbamylation. As aggregation and cross-linking of fibrin monomers rely on lysine residues, it is likely that carbamylation impacts fibrinogen processing...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28374316/modulation-of-protein-fragmentation-through-carbamylation-of-primary-amines
#13
Sylvester M Greer, Dustin D Holden, Ryan Fellers, Neil L Kelleher, Jennifer S Brodbelt
We evaluate the impact of carbamylation of the primary amines of the side-chains of Lys and the N-termini on the fragmentation of intact protein ions and the chromatographic properties of a mixture of E. coli ribosomal proteins. The fragmentation patterns of the six unmodified and carbamylated proteins obtained by higher energy collision dissociation (HCD) and ultraviolet photodissociation (UVPD) were compared. Carbamylation significantly reduced the total number of protons retained by the protein owing to the conversion of basic primary amines to non-basic carbamates...
April 3, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28302542/clinical-implications-associated-with-the-posttranslational-modification-induced-functional-impairment-of-albumin-in-oxidative-stress-related-diseases
#14
REVIEW
Hiroshi Watanabe, Tadashi Imafuku, Masaki Otagiri, Toru Maruyama
Recent research findings indicate that the posttranslational modification of human serum albumin (HSA) such as oxidation, glycation, truncation, dimerization, and carbamylation is related to certain types of diseases. We report herein on a simple and rapid analytical method, using an electrospray ionization time-of-flight mass spectrometry technique, that allows posttranslational modifications of HSA to be quantitatively and qualitatively evaluated with a high degree of sensitivity. In patients with chronic liver disease, chronic renal disease, and diabetes mellitus, an increase in the level of oxidized cysteine-34 (Cys-34) of HSA accompanied by a decrease in the level of reduced Cys-34 was observed...
March 14, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28296337/anti-carbamylated-protein-antibodies-in-rheumatoid-arthritis-patients-are-reactive-to-specific-epitopes-of-the-human-fibrinogen-%C3%AE-chain
#15
Jonathan D Jones, B JoNell Hamilton, William F C Rigby
OBJECTIVE: Anti-carbamylated protein antibodies (ACarPA) are associated with rheumatoid arthritis (RA) risk and severity and are primarily directed against fibrinogen. The lack of understanding of ACarPA reactivity has limited analysis of their immunopathogenic associations in RA. To address this shortcoming, we mapped ACarPA epitope reactivity in RA patient sera. METHODS: Immunoblotting identified a patient serum with specific reactivity to carbamylated human fibrinogen β-chain...
March 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28291659/identification-of-carbamylated-alpha-1-anti-trypsin-a1at-as-an-antigenic-target-of-anti-carp-antibodies-in-patients-with-rheumatoid-arthritis
#16
Marije K Verheul, Alvin Yee, Andrea Seaman, George M Janssen, Peter A van Veelen, Jan W Drijfhout, Rene E M Toes, Michael Mahler, Leendert A Trouw
In 2011 a novel autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, was described in rheumatoid arthritis (RA) patients. Anti-CarP antibody positivity associates with a more severe disease course, is observed years before disease onset, and may predict the development of RA in arthralgia patients. Although many clinical observations have been carried out, information on the antigenic targets of anti-CarP antibodies is limited. Most studies on anti-CarP antibodies utilize an ELISA-based assay with carbamylated fetal calf serum (Ca-FCS) as antigen, a complex mixture of proteins...
March 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28290250/synthesis-and-ativiral-activity-of-5-benzylthio-4-carbamyl-1-2-3-triazoles-against-human-cytomegalovirus-cmv-and-varicella-zoster-virus-vzv
#17
Yi-Ning Wen, Zhi-Feng Zhang, Ning-Ning Liu, Graciela Andrei, Robert Snoeck, Yu-Hong Xiang, Dominique Schols, Xue Chen, Zhuo-Yong Zhang, Qing-Shan Zhang, Qin-Pei Wu
BACKGROUND: All of clinic drugs for herpesvirus infections exhibit high toxicity and suffer from significant drug-resistantance. There is a great need for the development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action. METHODS: A series of novel 5-(benzylthio)-1H-1,2,3- triazole-4-carboxamides were efficiently synthesized and EC50 values against human cytomegalovirus (HCMV), varicella-zoster virus (VZV) and herpes simplex virus (HSV) were evaluated in vitro...
March 7, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28275265/beyond-citrullination-other-post-translational-protein-modifications-in-rheumatoid-arthritis
#18
REVIEW
Leendert A Trouw, Theo Rispens, Rene E M Toes
The presence of autoantibodies is one of the hallmarks of rheumatoid arthritis (RA). In the past few decades, rheumatoid factors (autoantibodies that recognize the Fc-tail of immunoglobulins) as well as anti-citrullinated protein antibodies (ACPAs) have been studied intensively. ACPAs recognize post-translationally modified proteins in which the amino acid arginine has been converted into a citrulline. More recently, other autoantibody systems recognizing post-translationally modified proteins have also gained attention, including autoantibodies recognizing fragmented immunoglobulin (anti-hinge antibodies), autoantibodies recognizing acetylated proteins and autoantibodies recognizing proteins that are modified by adducts formed under oxidative stress...
June 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28183721/carbamylation-of-vimentin-is-inducible-by-smoking-and-represents-an-independent-autoantigen-in-rheumatoid-arthritis
#19
Caroline Ospelt, Holger Bang, Eugen Feist, Giovanni G 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
#20
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
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