Carbamylation of Integrin
carbamylation
chronic hemodialysis
chronic kidney failure
coagulation
end stage renal disease
platelets
protein carbamylation
uremia
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
04
01
2022
accepted:
05
06
2022
pubmed:
30
8
2022
medline:
14
1
2023
entrez:
29
8
2022
Statut:
ppublish
Résumé
Bleeding diatheses, common among patients with ESKD, can lead to serious complications, particularly during invasive procedures. Chronic urea overload significantly increases cyanate concentrations in patients with ESKD, leading to carbamylation, an irreversible modification of proteins and peptides. To investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin Carbamylation inhibited platelet activation, adhesion, and aggregation. Patients on hemodialysis exhibited significantly reduced activation of Carbamylation of
Sections du résumé
BACKGROUND
Bleeding diatheses, common among patients with ESKD, can lead to serious complications, particularly during invasive procedures. Chronic urea overload significantly increases cyanate concentrations in patients with ESKD, leading to carbamylation, an irreversible modification of proteins and peptides.
METHODS
To investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin
RESULTS
Carbamylation inhibited platelet activation, adhesion, and aggregation. Patients on hemodialysis exhibited significantly reduced activation of
CONCLUSIONS
Carbamylation of
Identifiants
pubmed: 36038265
pii: 00001751-202210000-00012
doi: 10.1681/ASN.2022010013
pmc: PMC9528322
doi:
Substances chimiques
Platelet Glycoprotein GPIIb-IIIa Complex
0
Fibrinogen
9001-32-5
Amino Acids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1841-1856Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM118112
Pays : United States
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Références
Hedges SJ, Dehoney SB, Hooper JS, Amanzadeh J, Busti AJ: Evidence-based treatment options for uremic bleeding. Nat Clin Pract Nephrol 3: 130–153, 2007
Noris M, Remuzzi G: Uremic bleeding: Closing the circle after 30 years of controversies? Blood 94: 2569–2574, 1999
Lutz J, Menke J, Sollinger D, Schinzel H, Thürmel K: Haemostasis in chronic kidney disease. Nephrol Dial Transplant 29: 29–40, 2014
Kuo C-C, Kuo H-W, Lee I-M, Lee C-T, Yang C-Y: The risk of upper gastrointestinal bleeding in patients treated with hemodialysis: A population-based cohort study. BMC Nephrol 14: 15, 2013
Jalal DI, Chonchol M, Targher G: Disorders of hemostasis associated with chronic kidney disease. Semin Thromb Hemost 36: 34–40, 2010
van Bladel ER, de Jager RL, Walter D, Cornelissen L, Gaillard CA, Boven LA, et al.: Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro. BMC Nephrol 13: 127, 2012
Kaw D, Malhotra D: Platelet dysfunction and end-stage renal disease. Semin Dial 19: 317–322, 2006
Joist JH, George JN: Hemostatic abnormalities in liver and renal disease. In: Hemostasis and Thrombosis: Basic principles and clinical practice, edited by Colman RW, Hirsh J, Marder VJ, Philadelphia, PA, Lippincott Williams & Wilkins, 2001, pp 955–973
Linthorst GE, Avis HJ, Levi M: Uremic thrombocytopathy is not about urea. J Am Soc Nephrol 21: 753–755, 2010
Galbusera M, Remuzzi G, Boccardo P: Treatment of bleeding in dialysis patients. Semin Dial 22: 279–286, 2009
Molino D, De Lucia D, Gaspare De Santo N: Coagulation disorders in uremia. Semin Nephrol 26: 46–51, 2006
Cohen G, Hörl WH: Immune dysfunction in uremia—an update. Toxins (Basel) 4: 962–990, 2012
Vanholder R, Pletinck A, Schepers E, Glorieux G: Biochemical and clinical impact of organic uremic retention solutes: A comprehensive update. Toxins (Basel) 10: 33, 2018
Lisowska-Myjak B: Uremic toxins and their effects on multiple organ systems. Nephron Clin Pract 128: 303–311, 2014
Delanghe S, Delanghe JR, Speeckaert R, Van Biesen W, Speeckaert MM: Mechanisms and consequences of carbamoylation. Nat Rev Nephrol 13: 580–593, 2017
Verbrugge FH, Tang WH, Hazen SL: Protein carbamylation and cardiovascular disease. Kidney Int 88: 474–478, 2015
Kalim S, Karumanchi SA, Thadhani RI, Berg AH: Protein carbamylation in kidney disease: Pathogenesis and clinical implications. Am J Kidney Dis 64: 793–803, 2014
Kraus LM, Gaber L, Handorf CR, Marti H-P, Kraus AP Jr: Carbamoylation of glomerular and tubular proteins in patients with kidney failure: A potential mechanism of ongoing renal damage. Swiss Med Wkly 131: 139–4, 2001
Vanholder R, Gryp T, Glorieux G: Urea and chronic kidney disease: The comeback of the century? (in uraemia research). Nephrol Dial Transplant 33: 4–12, 2018
Shaykh M, Pegoraro AA, Mo W, Arruda JA, Dunea G, Singh AK: Carbamylated proteins activate glomerular mesangial cells and stimulate collagen deposition. J Lab Clin Med 133: 302–308, 1999
Trepanier DJ, Thibert RJ, Draisey TF, Caines PS: Carbamylation of erythrocyte membrane proteins: An in vitro and in vivo study. Clin Biochem 29: 347–355, 1996
Pieniazek A, Gwoździński K: Carbamylation of proteins leads to alterations in the membrane structure of erythrocytes. Cell Mol Biol Lett 8: 127–131, 2003
Mun K-C, Kim H-C, Kwak C-S: Cyanate as a hemolytic factor. Ren Fail 22: 809–814, 2000
Kraus LM, Elberger AJ, Handorf CR, Pabst MJ, Kraus AP Jr: Urea-derived cyanate forms epsilon-amino-carbamoyl-lysine (homocitrulline) in leukocyte proteins in patients with end-stage renal disease on peritoneal dialysis. J Lab Clin Med 123: 882–891, 1994
Broos K, De Meyer SF, Feys HB, Vanhoorelbeke K, Deckmyn H: Blood platelet biochemistry. Thromb Res 129: 245–249, 2012
Gawaz MP, Dobos G, Späth M, Schollmeyer P, Gurland HJ, Mujais SK: Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease. J Am Soc Nephrol 5: 36–46, 1994
Małyszko J, Małyszko JS, Myśliwiec M, Buczko W: Hemostasis in chronic renal failure. Rocz Akad Med Bialymst 50: 126–131, 2005
Monroe DM, Hoffman M, Roberts HR: Platelets and thrombin generation. Arterioscler Thromb Vasc Biol 22: 1381–1389, 2002
Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR: Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 103: 879–887, 1999
De Candia E: Mechanisms of platelet activation by thrombin: A short history. Thromb Res 129: 250–256, 2012
Binder V, Bergum B, Jaisson S, Gillery P, Scavenius C, Spriet E, et al.: Impact of fibrinogen carbamylation on fibrin clot formation and stability. Thromb Haemost 117: 899–910, 2017
Jaisson S, Desmons A, Doué M, Gorisse L, Pietrement C, Gillery P: Measurement of homocitrulline, a carbamylation-derived product, in serum and tissues by LC-MS/MS. Curr Protoc Protein Sci 92: e56, 2018
Bicker KL, Subramanian V, Chumanevich AA, Hofseth LJ, Thompson PR: Seeing citrulline: Development of a phenylglyoxal-based probe to visualize protein citrullination. J Am Chem Soc 134: 17015–17018, 2012
Litvinov RI, Barsegov V, Schissler AJ, Fisher AR, Bennett JS, Weisel JW, et al.: Dissociation of bimolecular αIIbβ3-fibrinogen complex under a constant tensile force. Biophys J 100: 165–173, 2011
Zhu J, Luo B-H, Xiao T, Zhang C, Nishida N, Springer TA: Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 32: 849–861, 2008
Gawaz M, Neumann F-J, Schomig A: Evaluation of platelet membrane glycoproteins in coronary artery disease: Consequences for diagnosis and therapy. Circulation 99: E1–E11, 1999
Kalim S, Ortiz G, Trottier CA, Deferio JJ, Karumanchi SA, Thadhani RI, et al.: The effects of parenteral amino acid therapy on protein carbamylation in maintenance hemodialysis patients. J Ren Nutr 25: 388–392, 2015
De Cuyper IM, Meinders M, van de Vijver E, de Korte D, Porcelijn L, de Haas M, et al.: A novel flow cytometry-based platelet aggregation assay. Blood 121: e70–e80, 2013
Koeth RA, Kalantar-Zadeh K, Wang Z, Fu X, Tang WH, Hazen SL: Protein carbamylation predicts mortality in ESRD. J Am Soc Nephrol 24: 853–861, 2013
El-Gamal D, Holzer M, Gauster M, Schicho R, Binder V, Konya V, et al.: Cyanate is a novel inducer of endothelial icam-1 expression. Antioxid Redox Signal 16: 129–137, 2012
Blackmore DJ, Elder WJ, Bowden CH: Urea distribution in renal failure. J Clin Pathol 16: 235–243, 1963
El-Gamal D, Rao SP, Holzer M, Hallström S, Haybaeck J, Gauster M, et al.: The urea decomposition product cyanate promotes endothelial dysfunction. Kidney Int 86: 923–931, 2014
Kaufman RM: Platelets: Testing, dosing and the storage lesion--recent advances. Hematology Am Soc Hematol Educ Program 2006: 492–496, 2006
Papadaki S, Sidiropoulou S, Moschonas IC, Tselepis AD: Factor Xa and thrombin induce endothelial progenitor cell activation. The effect of direct oral anticoagulants. Platelets 32: 807–814, 2021
Nieman MT, Schmaier AH: Interaction of thrombin with PAR1 and PAR4 at the thrombin cleavage site. Biochemistry 46: 8603–8610, 2007
Mumford AD, Frelinger AL 3rd, Gachet C, Gresele P, Noris P, Harrison P, et al.: A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders. Thromb Haemost 114: 14–25, 2015
Fullard JF: The role of the platelet glycoprotein IIb/IIIa in thrombosis and haemostasis. Curr Pharm Des 10: 1567–1576, 2004
Ma Y, Tonelli M, Unsworth LD: Effect of carbamylation on protein structure and adsorption to self-assembled monolayer surfaces. Colloids Surf B Biointerfaces 203: 111719, 2021
Desmons A, Okwieka A, Doué M, Gorisse L, Vuiblet V, Pietrement C, et al.: Proteasome-dependent degradation of intracellular carbamylated proteins. Aging (Albany NY) 11: 3624–3638, 2019
Chinthalapudi K, Rangarajan ES, Izard T: The interaction of talin with the cell membrane is essential for integrin activation and focal adhesion formation. Proc Natl Acad Sci U S A 115: 10339–10344, 2018
Zhang P, Azizi L, Kukkurainen S, Gao T, Baikoghli M, Jacquier MC, et al.: Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding. Proc Natl Acad Sci U S A 117: 32402–32412, 2020
Botero JP, Lee K, Branchford BR, Bray PF, Freson K, Lambert MP, et al.: ClinGen Platelet Disorder Variant Curation Expert Panel: Glanzmann thrombasthenia: Genetic basis and clinical correlates. Haematologica 105: 888–894, 2020
Berg AH, Drechsler C, Wenger J, Buccafusca R, Hod T, Kalim S, et al.: Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure. Sci Transl Med 5: 175ra29, 2013
Tucker KL, Sage T, Gibbins JM: Clot retraction. Methods Mol Biol 788: 101–107, 2012
Metharom P, Berndt MC, Baker RI, Andrews RK: Current state and novel approaches of antiplatelet therapy. Arterioscler Thromb Vasc Biol 35: 1327–1338, 2015
Aksu HU, Oner E, Celik O, Isiksacan N, Aksu H, Uzun S, et al.: Aspirin resistance in patients undergoing hemodialysis and effect of hemodialysis on aspirin resistance. Clin Appl Thromb Hemost 21: 82–86, 2015