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Homocitrullination

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https://www.readbyqxmd.com/read/29030163/metabolites-related-to-renal-function-immune-activation-and-carbamylation-are-associated-with-muscle-composition-in-older-adults
#1
Michael S Lustgarten, Roger A Fielding
Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM)...
October 10, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28992314/nutritional-therapy-reduces-protein-carbamylation-through-urea-lowering-in-chronic-kidney-disease
#2
Biagio R Di Iorio, Stefania Marzocco, Antonio Bellasi, Emanuele De Simone, Fabrizio Dal Piaz, Maria Teresa Rocchetti, Carmela Cosola, Lucia Di Micco, Loreto Gesualdo
Background: Protein carbamylation is one of the non-enzymatic reactions involved in protein molecular ageing. We sought to investigate the relationship between urea levels and protein carbamylation, and whether a Mediterranean diet (MD) and a very low protein diet (VLPD) reduce protein carbamylation through reduction in urea levels in patients with chronic kidney disease (CKD). Methods: This is a prospective, randomized, crossover controlled trial that investigated 60 patients with CKD grades 3B-4 (46 males, mean age of 67 years)...
July 11, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28971980/metabolomic-alterations-associated-with-cause-of-ckd
#3
Morgan E Grams, Adrienne Tin, Casey M Rebholz, Tariq Shafi, Anna Köttgen, Ronald D Perrone, Mark J Sarnak, Lesley A Inker, Andrew S Levey, Josef Coresh
BACKGROUND AND OBJECTIVES: Causes of CKD differ in prognosis and treatment. Metabolomic indicators of CKD cause may provide clues regarding the different physiologic processes underlying CKD development and progression. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Metabolites were quantified from serum samples of participants in the Modification of Diet in Renal Disease (MDRD) Study, a randomized controlled trial of dietary protein restriction and BP control, using untargeted reverse phase ultraperformance liquid chromatography tandem mass spectrometry quantification...
November 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28945351/metabolically-derived-lysine-acylations-and-neighboring-modifications-tune-the-binding-of-the-bet-bromodomains-to-histone-h4
#4
COMPARATIVE STUDY
Michael D Olp, Nan Zhu, Brian C Smith
Recent proteomic studies discovered histone lysines are modified by acylations beyond acetylation. These acylations derive from acyl-CoA metabolites, potentially linking metabolism to transcription. Bromodomains bind lysine acylation on histones and other nuclear proteins to influence transcription. However, the extent bromodomains bind non-acetyl acylations is largely unknown. Also unclear are the effects of neighboring post-translational modifications, especially within heavily modified histone tails. Using peptide arrays, binding assays, sucrose gradients, and computational methods, we quantified 10 distinct acylations for binding to the bromodomain and extraterminal domain (BET) family...
October 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28943354/hydroxyhomocitrulline-is-a-collagen-specific-carbamylation-mark-that-affects-cross-link-formation
#5
Yuki Taga, Keisuke Tanaka, Chieko Hamada, Masashi Kusubata, Kiyoko Ogawa-Goto, Shunji Hattori
Carbamylation is a non-enzymatic post-translational modification that physiologically occurs during aging and is a risk factor for various diseases. The most common product of carbamylation is homocitrulline (HCit), where a lysine (Lys) amino group has reacted with urea-derived cyanate. HCit has recently been detected in collagen; however, given that 15%-90% of total Lys in collagen is hydroxylated, it is unclear how hydroxylation affects collagen carbamylation. Here, we identified a collagen-specific carbamylation product, hydroxyhomocitrulline (HHCit), and showed that high levels of HHCit are correlated with age in rat tissue collagen and in vivo carbamylation in mice, as well as with the decline of kidney function in the serum of dialysis patients...
October 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28865468/brain-ureido-degenerative-protein-modifications-are-associated-with-neuroinflammation-and-proteinopathy-in-alzheimer-s-disease-with-cerebrovascular-disease
#6
Xavier Gallart-Palau, Aida Serra, Benjamin Sian Teck Lee, Xue Guo, Siu Kwan Sze
BACKGROUND: Brain degenerative protein modifications (DPMs) are associated with the apparition and progression of dementia, and at the same time, Alzheimer's disease with cerebrovascular disease (AD + CVD) is the most prevalent form of dementia in the elder population. Thus, understanding the role(s) of brain DPMs in this dementia subtype may provide novel insight on the disease pathogenesis and may aid on the development of novel diagnostic and therapeutic tools. Two essential DPMs known to promote inflammation in several human diseases are the ureido DPMs (uDPMs) arginine citrullination and lysine carbamylation, although they have distinct enzymatic and non-enzymatic origins, respectively...
September 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28757635/mechanisms-and-consequences-of-carbamoylation
#7
REVIEW
Sigurd Delanghe, Joris R Delanghe, Reinhart Speeckaert, Wim Van Biesen, Marijn M Speeckaert
Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term "carbamylation" in the literature, carbamylation refers to a different chemical reaction (the reversible interaction of CO2 with α and ε-amino groups of proteins). Depending on the altered molecule (for example, collagen, erythropoietin, haemoglobin, low-density lipoprotein or high-density lipoprotein), carbamoylation can have different pathophysiological effects...
September 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28690125/carbamylation-is-a-competitor-of-glycation-for-protein-modification-in-vivo
#8
C Nicolas, S Jaisson, L Gorisse, F J Tessier, C Niquet-Léridon, P Jacolot, C Pietrement, P Gillery
AIM: Chronic kidney disease (CKD) and diabetes mellitus are two diseases that accelerate protein molecular ageing through carbamylation and glycation reactions, characterized by the binding of urea-derived isocyanic acid and of sugars on proteins, respectively. These two reactions target the same protein amino groups and, thus, compete with each other. Such competition may arise especially in diabetic patients with nephropathy. This study aimed to evaluate their potential competitive effects in vitro and under conditions reproducing CKD and/or diabetes in vivo...
July 6, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28626469/serum-amino-acid-profiles-in-normal-subjects-and-in-patients-with-or-at-risk-of-alzheimer-dementia
#9
Gaetano Corso, Adriana Cristofano, Nadia Sapere, Giancarlo la Marca, Antonella Angiolillo, Michela Vitale, Roberto Fratangelo, Teresa Lombardi, Carola Porcile, Mariano Intrieri, Alfonso Di Costanzo
BACKGROUND/AIMS: Abnormalities in the plasma amino acid profile have been reported in Alzheimer disease (AD), but no data exist for the prodromal phase characterized by subjective memory complaint (SMC). It was our aim to understand if serum amino acid levels change along the continuum from normal to AD, and to identify possible diagnostic biomarkers. METHODS: Serum levels of 15 amino acids and 2 organic acids were determined in 4 groups of participants - 29 with probable AD, 18 with mild cognitive impairment (MCI), 24 with SMC, and 46 cognitively healthy subjects (HS) - by electrospray tandem mass spectrometry...
January 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/28598783/anti-homocitrullinated-protein-antibody-isotype-usage-in-rheumatoid-arthritis-and-their-unaffected-first-degree-relatives
#10
David A Bell, Sallie Elhayek, Ewa Cairns, Lillian Barra
OBJECTIVES: The majority of rheumatoid arthritis (RA) patients express anti-citrullinated protein antibodies (ACPA). Unaffected first-degree relatives of RA patients (FDR) also express ACPA, commonly of the IgA isotype. IgG anti-homocitrullinated/carbamylated protein antibodies (AHCPA) have been detected in both RA and FDR. It is unknown whether other isotypes are expressed. We aim to investigate the AHCPA isotype profile in unaffected FDR of RA patients. METHODS: The enrolled subjects were examined by a rheumatologist...
June 5, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28382370/impact-of-fibrinogen-carbamylation-on-fibrin-clot-formation-and-stability
#11
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...
May 3, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28296337/brief-report-anti-carbamylated-protein-antibodies-in-rheumatoid-arthritis-patients-are-reactive-with-specific-epitopes-of-the-human-fibrinogen-%C3%AE-chain
#12
Jonathan D Jones, B JoNell Hamilton, William F C Rigby
OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are associated with the risk and severity of rheumatoid arthritis (RA) and are primarily directed against fibrinogen. The lack of understanding of anti-CarP antibody reactivity has limited analysis of the immunopathogenic associations in RA. To address this shortcoming, we mapped anti-CarP antibody epitope reactivity in RA patient sera. METHODS: Immunoblotting identified a patient serum sample with specific reactivity to the carbamylated human fibrinogen β-chain...
July 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
#13
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/28183721/carbamylation-of-vimentin-is-inducible-by-smoking-and-represents-an-independent-autoantigen-in-rheumatoid-arthritis
#14
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...
July 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28122695/environmental-enteric-dysfunction-is-associated-with-carnitine-deficiency-and-altered-fatty-acid-oxidation
#15
Richard D Semba, Indi Trehan, Ximin Li, Ruin Moaddel, M Isabel Ordiz, Kenneth M Maleta, Klaus Kraemer, Michelle Shardell, Luigi Ferrucci, Mark Manary
BACKGROUND: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. METHODS: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test...
March 2017: EBioMedicine
https://www.readbyqxmd.com/read/27986757/cyanate-impaired-angiogenesis-association-with-poor-coronary-collateral-growth-in-patients-with-stable-angina-and-chronic-total-occlusion
#16
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/27765067/rheumatoid-arthritis-antigens-homocitrulline-and-citrulline-are-generated-by-local-myeloperoxidase-and-peptidyl-arginine-deiminases-2-3-and-4-in-rheumatoid-nodule-and-synovial-tissue
#17
Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
BACKGROUND: Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. METHOD: Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and homocitrulline contents using HPLC...
October 20, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27587397/eosinophil-peroxidase-catalyzed-protein-carbamylation-participates-in-asthma
#18
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/27323772/antimodified-protein-antibody-response-pattern-influences-the-risk-for-disease-relapse-in-patients-with-rheumatoid-arthritis-tapering-disease-modifying-antirheumatic-drugs
#19
Camille P Figueiredo, Holger Bang, Jayme Fogagnolo Cobra, Matthias Englbrecht, Axel J Hueber, Judith Haschka, Bernhard Manger, Arnd Kleyer, Michaela Reiser, Stephanie Finzel, Hans-Peter Tony, Stefan Kleinert, Joerg Wendler, Florian Schuch, Monika Ronneberger, Martin Feuchtenberger, Martin Fleck, Karin Manger, Wolfgang Ochs, Matthias Schmitt-Haendle, Hanns-Martin Lorenz, Hubert Nuesslein, Rieke Alten, Joerg Henes, Klaus Krueger, Jürgen Rech, Georg Schett
OBJECTIVE: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy. METHODS: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study...
February 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27302313/homocitrulline-as-marker-of-protein-carbamylation-in-hemodialyzed-patients
#20
Stéphane Jaisson, Isabelle Kazes, Aurore Desmons, Fouad Fadel, Jean-Baptiste Oudart, Izabella C R Dos Santos-Weiss, Hervé Millart, Fatouma Touré, Philippe Rieu, Philippe Gillery
BACKGROUND: Homocitrulline (HCit) is a carbamylation-derived product (CDP) that has been identified as a valuable biomarker of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of this study was to determine whether initiation of hemodialysis therapy (HD) could induce variations of HCit concentrations in CKD patients. METHODS: Serum HCit concentrations were determined by LC-MS/MS in CKD patients (n=108) just before (M0) and six months (M6) after the initiation of HD therapy...
September 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
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