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Carbamylation

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27771289/a-novel-uplc-ms-ms-based-method-to-determine-the-activity-of-n-acetylglutamate-synthase-in-liver-tissue
#7
Marli Dercksen, Marinus Duran, Lodewijk IJlst, Wim Kulik, Jos P N Ruiter, Arno van Cruchten, Mendel Tuchman, Ronald J A Wanders
BACKGROUND: N-acetylglutamate synthase (NAGS) plays a key role in the removal of ammonia via the urea cycle by catalyzing the synthesis of N-acetylglutamate (NAG), the obligatory cofactor in the carbamyl phosphate synthetase 1 reaction. Enzymatic analysis of NAGS in liver homogenates has remained insensitive and inaccurate, which prompted the development of a novel method. METHODS: UPLC-MS/MS was used in conjunction with stable isotope (N-acetylglutamic-2,3,3,4,4-d5 acid) dilution for the quantitative detection of NAG produced by the NAGS enzyme...
October 13, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27768275/integrating-weak-anion-exchange-and-ultraviolet-photodissociation-mass-spectrometry-with-strategic-modulation-of-peptide-basicity-for-the-enrichment-of-sulfopeptides
#8
Michelle R Robinson, Jennifer S Brodbelt
Tyrosine sulfation is an important post-translational modification but remains difficult to detect in biological samples owing to its low stoichiometric abundance and the lack of effective enrichment methods. In the present study, weak anion exchange (WAX) is evaluated for the enrichment of sulfopeptides that have been modified via carbamylation to convert all primary amines to less basic carbamates. The decrease in basicity enhanced the binding of carbamylated sulfopeptides to WAX resin relative to non-sulfated peptides...
October 21, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27712781/carbamylated-low-density-lipoprotein-and-thrombotic-risk-in-chronic%C3%A2-kidney%C3%A2-disease
#9
W H Wilson Tang, Stanley L Hazen
No abstract text is available yet for this article.
October 11, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27712780/carbamylated-low-density-lipoproteins%C3%A2-induce-a-prothrombotic%C3%A2-state%C3%A2-via-lox-1-impact-on-arterial-thrombus-formation-in-vivo
#10
Erik W Holy, Alexander Akhmedov, Thimoteus Speer, Giovanni G Camici, Stephen Zewinger, Nicole Bonetti, Jürg H Beer, Thomas F Lüscher, Felix C Tanner
BACKGROUND: Carbamylation alters low-density lipoprotein (LDL) structure and is thought to promote vascular inflammation and dysfunction in patients with chronic kidney disease (CKD). OBJECTIVES: This study sought to determine whether carbamylated LDL (cLDL) exerts prothrombotic effects in vascular cells and platelets and whether cLDL enhances arterial thrombus formation in vivo. METHODS: LDL was isolated from healthy subjects or patients with CKD by sequential ultracentrifugation...
October 11, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27683146/post-translational-modifications-in-rheumatoid-arthritis-and-atherosclerosis-focus-on-citrullination-and-carbamylation
#11
Francesca Romana Spinelli, Arbi Pecani, Fabrizio Conti, Riccardo Mancini, Cristiano Alessandri, Guido Valesini
Coronary heart disease is the main cause of mortality in patients with rheumatoid arthritis (RA), a disease known to be associated with accelerated atherosclerosis. The role of inflammation and immunity in atherosclerotic process offers possible explanations for the increased cardiovascular risk in patients with RA. The immune response to citrullinated peptides has been extensively studied in RA; antibodies directed to citrullinated peptides are now a cornerstone for RA diagnosis. However, few studies have investigated the response to citrullinated peptides and the development of atherosclerotic plaque...
September 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27660725/optimization-of-urea-based-protein-extraction-from-formalin-fixed-paraffin-embedded-tissue-for-shotgun-proteomics
#12
Stephen A Luebker, Scott A Koepsell
Urea based protein extraction of formalin-fixed paraffin-embedded (FFPE) tissue provides the most efficient workflow for proteomics due to its compatibility with liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). This study optimizes the use of urea for proteomic analysis of clinical FFPE tissue. A series of protein extraction conditions manipulating temperature and buffer composition were compared to reduce carbamylation introduced by urea and increase protein detection...
2016: International Journal of Proteomics
https://www.readbyqxmd.com/read/27618024/increased-serum-levels-of-anti-carbamylated-78-kda-glucose-regulated-protein-antibody-in-patients-with-rheumatoid-arthritis
#13
Hui-Chun Yu, Pei-Hsuan Lai, Ning-Sheng Lai, Hsien-Bin Huang, Malcolm Koo, Ming-Chi Lu
The objective of this study was to investigate the presence and titer of anti-carbamylated 78-kDa glucose-regulated protein (anti-CarGRP78) antibody in serum from controls, and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Thirty-three RA patients, 20 SLE patients, 20 pSS patients, and 20 controls were enrolled from our outpatient clinic. GRP78 was cloned and carbamylated. Serum titers of anti- cyclic citrullinated peptides (anti-CCP), anti-GRP78, and anti-CarGRP78 were measured with an enzyme-linked immunosorbent assay...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27615169/-protein-carbamylation-when-protein-and-chronologic-ageings-meet
#14
Laëtitia Gorisse, Stéphane Jaisson, Christine Pietrement, Philippe Gillery
No abstract text is available yet for this article.
August 2016: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/27587397/eosinophil-peroxidase-catalyzed-protein-carbamylation-participates-in-asthma
#15
Zeneng Wang, Joseph A DiDonato, Jennifer Buffa, Suzy A Comhair, Mark A Aronica, Raed A Dweik, Nancy A Lee, James J Lee, Mary Jane Thomassen, Mani Kavuru, Serpil C Erzurum, Stanley L Hazen
The biochemical mechanisms through which eosinophils contribute to asthma pathogenesis are unclear. Here we show eosinophil peroxidase (EPO), an abundant granule protein released by activated eosinophils, contributes to characteristic asthma-related phenotypes through oxidative posttranslational modification (PTM) of proteins in asthmatic airways through a process called carbamylation. Using a combination of studies we now show EPO uses plasma levels of the pseudohalide thiocyanate (SCN(-)) as substrate to catalyze protein carbamylation, as monitored by PTM of protein lysine residues into N(ϵ)-carbamyllysine (homocitrulline), and contributes to the pathophysiological sequelae of eosinophil activation...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27543755/proteins-and-their-modifications-in-a-medieval-mummy
#16
Ivan Mikšík, Pavla Sedláková, Statis Pataridis, Federica Bortolotti, Rossella Gottardo
Proteins and their modifications of the natural mummy of Cangrande della Scala (Prince of Verona, Northern Italy, 1291-1329) were studied. The nano-LC-Q-TOF analysis of samples of rib bone and muscle from the mummy showed the presence of different proteins including Types I, III, IV, V, and XI collagen, hemoglobin (subunits alpha and beta), ferritin, biglycan, vitronectin, prothrombin, and osteocalcin. The structure of Type I and Type III collagen was deeply studied to evaluate the occurrence of modifications in comparison with Type I and Type III collagen coming from tissues of recently died people...
November 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27541284/neuroprotection-and-cd131-gdnf-akt-pathway-of-carbamylated-erythropoietin-in-hypoxic-neurons
#17
Jing Ding, Jing Wang, Qin-Ying Li, Jie-Zhong Yu, Cun-Gen Ma, Xin Wang, Chuan-Zhen Lu, Bao-Guo Xiao
Carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to neuroprotective effects without erythropoiesis. However, little is known about molecular mechanisms behind CEPO-mediated neuroprotection. In primary neurons with oxygen-glucose deprivation (OGD) and mice with hypoxia-reoxygenation, the neuroprotection and possible molecular mechanism of CEPO were performed by immunohistochemistry and immunocytochemistry, Western blot, RT-PCR, and ELISA. The comparisons were analyzed by ANOVA followed by unpaired two-tailed Student's t test...
August 19, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27537849/anti-carbamylated-protein-antibodies-as-a-reproducible-independent-type-of-rheumatoid-arthritis-autoantibodies
#18
Ariana Montes, Cristina Regueiro, Eva Perez-Pampin, Maria Dolores Boveda, Juan J Gomez-Reino, Antonio Gonzalez
A large fraction of the patients with rheumatoid arthritis (RA) develop specific autoantibodies, which until recently were only of two types, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). We aimed to replicate important findings about a recently described third type of specific autoantibodies, anti-carbamylated protein (anti-CarP) antibodies, because they have been described based only in the homemade ELISA from a single laboratory. Our study included 520 patients with established RA and 278 healthy controls of Spanish ancestry and it was done with an independently performed ELISA...
2016: PloS One
https://www.readbyqxmd.com/read/27513925/equilibrium-dynamics-of-%C3%AE-n-methylamino-l-alanine-bmaa-and-its-carbamate-adducts-at-physiological-conditions
#19
David Zimmerman, Joy J Goto, Viswanathan V Krishnan
Elevated incidences of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) is associated with β-methylamino-L-alanine (BMAA), a non-protein amino acid. In particular, the native Chamorro people living in the island of Guam were exposed to BMAA by consuming a diet based on the cycad seeds. Carbamylated forms of BMAA are glutamate analogues. The mechanism of neurotoxicity of the BMAA is not completely understood, and BMAA acting as a glutamate receptor agonist may lead to excitotoxicity that interferes with glutamate transport systems...
2016: PloS One
https://www.readbyqxmd.com/read/27499369/ca-asp-bound-x-ray-structure-and-inhibition-of-bacillus-anthracis-dihydroorotase-dhoase
#20
Amy J Rice, Hao Lei, Bernard D Santarsiero, Hyun Lee, Michael E Johnson
Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis pathway and is responsible for the reversible cyclization of carbamyl-aspartate (Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes based on several structural characteristics, one of which is the length of the flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the enzyme activity. Here, we present the crystal structure of Class I Bacillus anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone of glycine in the shorter loop forming the necessary hydrogen bonds with the substrate, in place of the two threonines found in Class II DHOases...
October 1, 2016: Bioorganic & Medicinal Chemistry
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