Read by QxMD icon Read


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
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...
June 20, 2016: Annals of the Rheumatic Diseases
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
Ângela Zanatta, Marília Danyelle Nunes Rodrigues, Alexandre Umpierrez Amaral, Débora Guerini Souza, André Quincozes-Santos, Moacir Wajner
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection...
September 2016: Neurochemical Research
Evan Reed, Xia Jiang, Nastya Kharlamova, A Jimmy Ytterberg, Anca I Catrina, Lena Israelsson, Linda Mathsson-Alm, Monika Hansson, Lars Alfredsson, Johan Rönnelid, Karin Lundberg
BACKGROUND: In addition to anti-citrullinated protein antibodies (ACPAs), antibodies targeting carbamylated (i.e., homocitrullinated) proteins (anti-CarP antibodies) have been described in rheumatoid arthritis (RA). However, the extent to which anti-CarP antibodies are truly distinct from ACPA remains unclear, and few studies have focused on specific autoantigens. Here, we examine cross-reactivity between ACPA and anti-CarP antibodies, in the context of the candidate autoantigen α-enolase...
2016: Arthritis Research & Therapy
Sanna Turunen, Marja-Kaisa Koivula, Leila Risteli, Juha Risteli
The specificities and cross-reactions of antibodies induced by citrulline- and homocitrulline-containing proteins may give implications on the role of citrulline- and homocitrulline-binding antibodies in the pathogenesis and progression of rheumatoid arthritis (RA). Here we use rabbits as an experimental model of antibody development in RA. Thirty-two animals were immunized with peptide antigens containing either homocitrulline or citrulline. The sera were tested for binding to CCP and MCV antigens and to peptide sequences related to carboxyterminal telopeptides of type I and II collagens and containing arginine, citrulline, or homocitrulline...
April 21, 2016: Autoimmunity
Mona Ascha, Zeneng Wang, Mustafa S Ascha, Raed Dweik, Nizar N Zein, David Grove, J Mark Brown, Stephanie Marshall, Rocio Lopez, Ibrahim A Hanouneh
AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis (AH). METHODS: We prospectively recruited patients with cirrhosis from AH (n = 23) and those with cirrhosis with acute decompensation (AD) from etiologies other than alcohol (n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis...
April 8, 2016: World Journal of Hepatology
Laëtitia Gorisse, Christine Pietrement, Vincent Vuiblet, Christian E H Schmelzer, Martin Köhler, Laurent Duca, Laurent Debelle, Paul Fornès, Stéphane Jaisson, Philippe Gillery
Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties...
February 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
Alain Cantagrel, Yannick Degboé
Citrullination, carbamylation and oxidation are posttranslational modifications of proteins that produce neoepitopes. Rheumatoid arthritis (RA) is an autoimmune disease of which one distinctive feature is the development of B-cell-mediated immunity against these neoepitopes. Antibodies to citrullinated proteins (ACPAs) were identified nearly two decades ago and are now widely used in clinical practice. The identification of additional citrullinated proteins as potential autoantibody targets has suggested new pathophysiological hypotheses and prompted studies of potential associations with disease severity or specific disease patterns...
January 2016: Joint, Bone, Spine: Revue du Rhumatisme
Håkon Reikvam, Ida-Sofie Grønningsæter, Aymen Bushra Ahmed, Kimberley Hatfield, Øystein Bruserud
Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications. Capillary leak syndrome is a common early posttransplant complication where endothelial cell dysfunction probably contributes to the pathogenesis. In the present study we investigated whether the pretreatment serum metabolic profile reflects a risk of posttransplant capillary leak syndrome...
2015: Disease Markers
Aditya D Joshi, Mehnaz G Mustafa, Cheryl F Lichti, Cornelis J Elferink
The aryl hydrocarbon receptor (AhR), a regulator of xenobiotic toxicity, is a member of the eukaryotic Per-Arnt-Sim domain protein family of transcription factors. Recent evidence identified a novel AhR DNA recognition sequence called the nonconsensus xenobiotic response element (NC-XRE). AhR binding to the NC-XRE in response to activation by the canonical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in concomitant recruitment of carbamoyl phosphate synthase 1 (CPS1) to the NC-XRE. Studies presented here demonstrate that CPS1 is a bona fide nuclear protein involved in homocitrullination (hcit), including a key lysine residue on histone H1 (H1K34hcit)...
November 13, 2015: Journal of Biological Chemistry
Aurore Desmons, Stéphane Jaisson, Christine Pietrement, Philippe Rieu, Alain Wynckel, Philippe Gillery
BACKGROUND: Carbamylation is a non-enzymatic post-translational modification of proteins characterized by the addition of isocyanic acid to amino groups. As isocyanic acid mainly originates from the spontaneous dissociation of urea, carbamylation rate is increased during renal failure. The aim of the study was to evaluate serum homocitrulline (HCit), which results from the carbamylation of ε-amino groups of lysine (Lys) residues, in acute renal failure (ARF) and to determine if it could be useful for differentiating acute from chronic renal failure (CRF)...
January 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Diego Martinelli, Daria Diodato, Emanuela Ponzi, Magnus Monné, Sara Boenzi, Enrico Bertini, Giuseppe Fiermonte, Carlo Dionisi-Vici
BACKGROUND: Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical signs include intermittent episodes of vomiting, confusion or coma and hepatitis-like attacks. Alternatively, patients show a chronic course with aversion for protein rich foods, developmental delay/intellectual disability, myoclonic seizures, ataxia and pyramidal dysfunction...
2015: Orphanet Journal of Rare Diseases
Philippe Gillery, Stéphane Jaisson, Laëtitia Gorisse, Christine Pietrement
Carbamylation corresponds to the non-enzymatic binding of isocyanic acid, mainly derived from urea decomposition, on amino groups of proteins, and participates in their molecular aging. This process is increased during chronic kidney disease (CKD) because of hyperuremia, and in other pathologies like atherosclerosis, where isocyanic may be formed from thiocyanate by myeloperoxidase in atheroma plates. Carbamylation triggers structural and functional modifications of proteins, thus impairing their biological roles and their interactions with cells...
June 2015: Néphrologie & Thérapeutique
Ângela Zanatta, Carolina Maso Viegas, Fernanda Hermes Hickmann, Wagner de Oliveira Monteiro, Angela Sitta, Daniela de Moura Coelho, Carmen Regla Vargas, Guilhian Leipnitz, Moacir Wajner
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an inborn error of metabolism caused by a defect in the transport of ornithine (Orn) into mitochondrial matrix leading to accumulation of Orn, homocitrulline (Hcit), and ammonia. Affected patients present a variable clinical symptomatology, frequently associated with cerebellar symptoms whose pathogenesis is poorly known. Although in vitro studies reported induction of oxidative stress by the metabolites accumulating in HHH syndrome, so far no report evaluated the in vivo effects of these compounds on redox homeostasis in cerebellum...
August 2015: Cellular and Molecular Neurobiology
René E M Toes, Tom J W Huizinga
PURPOSE OF REVIEW: This article provides an update on the recent findings on autoantibodies to modified proteins in rheumatoid arthritis (RA). RECENT FINDINGS: In the past few years, the knowledge on the autoantibodies to citrullinated antigens has expanded considerably. More specifically, it is now clear that many different citrullinated protein antigens present in the synovial compartment can be recognized by anticitrullinated protein antibody (ACPA). This is most likely a consequence of the cross-reactivity the ACPA response displays to citrullinated proteins...
May 2015: Current Opinion in Rheumatology
Elena B Lugli, Raquel E S M Correia, Roman Fischer, Karin Lundberg, Ken R Bracke, Anna B Montgomery, Benedikt M Kessler, Guy G Brusselle, Patrick J Venables
INTRODUCTION: Smoking is a well-established risk factor for rheumatoid arthritis (RA), and it has been proposed that smoking-induced citrullination renders autoantigens immunogenic. To investigate this mechanism, we examined human lung tissue from 40 subjects with defined smoking status, with or without chronic obstructive pulmonary disease (COPD), and control tissues from other organs for citrullinated proteins and the deiminating enzymes peptidylarginine deiminase type-2 (PAD2) and -4 (PAD4)...
2015: Arthritis Research & Therapy
Sanna Turunen, Pekka Hannonen, Marja-Kaisa Koivula, Leila Risteli, Juha Risteli
INTRODUCTION: Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence. METHODS: A total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV)...
2015: Arthritis Research & Therapy
Stéphane Jaisson, Mohsen Kerkeni, Izabella C R Santos-Weiss, Faouzi Addad, Mohammed Hammami, Philippe Gillery
BACKGROUND: Carbamylation is a non-enzymatic post-translational modification of proteins that has been recently identified as a non-traditional risk factor for atherosclerosis. The aim of this study was to determine whether serum homocitrulline (HCit), a characteristic carbamylation-derived product, was related to the presence and the severity of coronary artery disease (CAD). METHODS: Forty-five control subjects and 109 patients were included in this cross-sectional study...
January 2015: Clinical Chemistry and Laboratory Medicine: CCLM
Catalin Koro, Ewa Bielecka, Anders Dahl-Knudsen, Jan J Enghild, Carsten Scavenius, Johan G Brun, Veronika Binder, Annelie Hellvard, Brith Bergum, Roland Jonsson, Jan Potempa, Anna M Blom, Piotr Mydel
Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG1 carbamylation under inflammatory conditions and the effects that this modification has on the ability of antibodies to trigger complement activation via the classical pathway. We found that the lysine residues of IgG1 are rapidly modified after brief exposure to CNO- ...
November 2014: European Journal of Immunology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"