Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 52, Issue 1

Issues

Post-translational modification derived products (PTMDPs): toxins in chronic diseases?

Philippe Gillery
  • Corresponding author
  • Laboratory of Pediatric Biology and Research, American Memorial Hospital, University Hospital of Reims, Reims, France
  • Laboratory of Medical Biochemistry and Molecular Biology, FRE CNRS/URCA N° 3481, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Stéphane Jaisson
  • Laboratory of Pediatric Biology and Research, American Memorial Hospital, University Hospital of Reims, Reims, France
  • Laboratory of Medical Biochemistry and Molecular Biology, FRE CNRS/URCA N° 3481, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-03-02 | DOI: https://doi.org/10.1515/cclm-2012-0880

Abstract

In living organisms, proteins are progressively modified by spontaneous non-enzymatic reactions generating many post-translational modification derived products (PTMDPs) which exert deleterious effects and may be considered endogenous toxins in diabetes mellitus and chronic renal failure. Non-enzymatic glycation, which refers to the spontaneous binding of reducing sugars to free amino groups, is increased in diabetes mellitus because of hyperglycemia and is amplified by oxidative processes (‘glycoxidation’). Glycoxidation leads to the formation of ‘advanced glycation end products’ (AGEs), together with products of other oxidative pathways. AGEs alter tissue organization and cell-protein interactions, mainly in the case of long-lived extracellular matrix proteins, and interact with membrane receptors, among which RAGE (receptor of AGEs), a multiligand receptor which triggers intracellular signaling pathways stimulating inflammatory functions. Another major protein modification, carbamylation, is increased in chronic renal failure, which may occur during the course of diabetes mellitus. Carbamylation is due to the binding of isocyanic acid on the α-NH2 extremity of proteins or amino acids, or on ε-NH2 lysine groups, generating homocitrulline, a potential biomarker in atherosclerosis. Isocyanic acid is formed in vivo either by spontaneous dissociation of urea or by myeloperoxidase action on thiocyanate. Carbamylated proteins exhibit altered properties. For example, carbamylated collagen is unable to stimulate oxidative functions of polymorphonuclear neutrophils but increases matrix metalloproteinase-9 production by monocytes. Lipoprotein functions are altered by carbamylation and may contribute to atherogenesis. Thus, the numerous PTMDPs may be considered both hallmarks of protein damage in chronic diseases and endogenous toxins acting at the molecular and cellular levels.

Keywords: carbamylation; chronic renal failure; diabetes mellitus; glycation; non-enzymatic post-translational modifications; uremic toxins

References

  • 1.

    Jaisson S, Gillery P. Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. Clin Chem 2010;56:1401–12.Web of SciencePubMedCrossrefGoogle Scholar

  • 2.

    Jaisson S, Pietrement C, Gillery P. Carbamylation derived products (CDPs): bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis. Clin Chem 2011;57:1499–505.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 3.

    D’Agati V, Schmidt AM. RAGE and the pathogenesis of chronic kidney disease. Nature Rev Nephrol 2010;6:352–60.CrossrefGoogle Scholar

  • 4.

    Ahmed N, Thornalley PJ. Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 2007;9:233–45.CrossrefWeb of SciencePubMedGoogle Scholar

  • 5.

    Gillery P. A history of HbA1c through Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2013;51:65–74.Google Scholar

  • 6.

    Mosca A, Lapolla A, Gillery P. Glycemic control in the clinical management of diabetic patients. Clin Chem Lab Med 2013;51:753–66.PubMedWeb of ScienceGoogle Scholar

  • 7.

    Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 2000;28;1708–16.Google Scholar

  • 8.

    Baynes JW. Chemical modification of proteins by lipids in diabetes. Clin Chem Lab Med 2003;41:1159–65.PubMedGoogle Scholar

  • 9.

    Witko-Sarsat V, Nguyen-Khoa T, Jungers P, Drueke TB, Descamps-Latscha B. Advanced oxidation protein products as a novel molecular basis of oxidative stress in uraemia. Nephrol Dial Transplant 1999;14(Suppl 1):76–8.Google Scholar

  • 10.

    Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006;114:597–605.Google Scholar

  • 11.

    Basta G. Receptor for advanced glycation endproducts and atherosclerosis: from basic mechanisms to clinical implications. Atherosclerosis 2008;196:9–21.Web of ScienceGoogle Scholar

  • 12.

    Takeuchi M, Yamagishi S. Involvement of toxic AGEs (TAGE) in the pathogenesis of diabetic vascular complications and Alzheimer’s disease. J Alzheimers Dis 2009;16:845–58.PubMedWeb of ScienceGoogle Scholar

  • 13.

    Vlassara H, Striker G. Glycotoxins in the diet promote diabetes and diabetic complications. Curr Diab Rep 2007;7:235–41.CrossrefPubMedGoogle Scholar

  • 14.

    Gillery P, Monboisse JC, Maquart FX, Borel JP. Glycation of proteins as a source of superoxide. Diab Metab 1988;14: 25–30.Google Scholar

  • 15.

    Bailey AJ, Paul RG, Knott L. Mechanisms of maturation and ageing of collagen. Mech Ageing Dev 1998;106:1–56.PubMedCrossrefGoogle Scholar

  • 16.

    Monboisse JC, Rittié L, Lamfarraj H, Garnotel R, Gillery P. In vitro glycoxidation alters the interactions between collagens and human polymorphonuclear leucocytes. Biochem J 2000;350:777–83.Google Scholar

  • 17.

    Touré F, Zahm JM, Garnotel R, Lambert E, Bonnet N, Schmidt AM, et al. Receptor for advanced glycation end products (RAGE) modulates neutrophil adhesion and migration on glycoxidated extracellular matrix. Biochem J 2008;416:255–61.Web of ScienceGoogle Scholar

  • 18.

    Thornalley PJ. Advanced glycation end products in renal failure. J Ren Nutr 2006;16:178–84.PubMedCrossrefGoogle Scholar

  • 19.

    Stark GR, Stein WH, Moore S. Reactions of the cyanate present in aqueous urea with aminoacids and proteins. J Biol Chem 1960;235:3177–81.Google Scholar

  • 20.

    Wang Z, Nicholls SJ, Rodriguez ER, Kummu O, Hörkkö S, Barnard J, et al. Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nat Med 2007;13:1167–84.Web of ScienceGoogle Scholar

  • 21.

    Roberts JM, Veres PR, Cochran AK, Warneke C, Burling IR, Yokelson RJ, et al. Isocyanic acid in the atmosphere and its possible link to smoke related health effects. Proc Natl Acad Sci USA 2011;108:8966–71.CrossrefWeb of ScienceGoogle Scholar

  • 22.

    Kraus LM, Kraus AP Jr. Carbamoylation of amino acids and proteins in uremia. Kidney Int Suppl 2001;78:S102–7.CrossrefGoogle Scholar

  • 23.

    Kraus LM, Jones MR, Kraus AP Jr. Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal disease managed by continuous ambulatory peritoneal dialysis: isolation, identification, and quantitation. J Lab Clin Med 1998;131:425–31.Google Scholar

  • 24.

    Kraus LM, Kraus AP Jr. The search for the uremic toxin: the case for carbamoylation of amino acids and proteins. Wien Klin Wochenschr 1998;110:521–30.PubMedGoogle Scholar

  • 25.

    Schreier SM, Hollaus M, Hermann M, Jirovetz L, Exner M, Kapiotis S, et al. Carbamoylated free amino acids in uremia: HOCl generates volatile protein modifying and cytotoxic oxidant species form N-carbamoyl-threonine but not threonine. Biochimie 2012;94:2441–7.Web of ScienceCrossrefGoogle Scholar

  • 26.

    Dengler TJ, Robertz-Vaupel GM, Dengler HJ. Albumin binding in uremia: quantitative assessment of inhibition by endogenous ligands and carbamylation of albumin. Eur J Clin Pharmacol 1992;43:491–9.PubMedCrossrefGoogle Scholar

  • 27.

    Jaisson S, Delevallée-Forte C, Touré F, Rieu P, Garnotel R, Gillery P. Carbamylated albumin is a potent inhibitor of polymorphonuclear neutrophil respiratory burst. FEBS Lett 2007;581:1509–13.Web of ScienceGoogle Scholar

  • 28.

    Gross ML, Piecha G, Bierhaus A, Hanke W, Henle, T, Schirmacher P, et al. Glycated and carbamylated albumin are more “nephrotoxic” than unmodified albumin in the amphibian kidney. Am J Physiol Renal Physiol 2011;301:F476–85.Web of ScienceGoogle Scholar

  • 29.

    Apostolov EO, Shah SV, Ok E, Basnakian AG. Carbamylated low-density lipoprotein induces monocyte adhesion to endothelial cells through intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Arterioscler Thromb Vasc Biol 2007;27:826–32.CrossrefWeb of ScienceGoogle Scholar

  • 30.

    Asci G, Basci A, Shah SV, Basnakian A, Toz H, Ozkahya M, et al. Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells. Nephrology 2008;13:480–6.Web of ScienceCrossrefGoogle Scholar

  • 31.

    Carracedo J, Merino A, Briceno C, Soriano S, Buendia P, Calleros L, et al. Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells. FASEB J 2011;25:1314–22.CrossrefWeb of SciencePubMedGoogle Scholar

  • 32.

    Holzer M, Birner-Gruenberger R, Stojakovic T, El-Gamal D, Binder V, Wadsack C, et al. Uremia alters HDL composition and function. J Am Soc Nephrol 2011;22:1631–41.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 33.

    Holzer M, Zangger K, El-Gamal D, Binder V, Curcic S, Konya V, et al. Myeloperoxidase-derived chlorinating species induce protein carbamylation through decomposition of thiocyanate and urea: novel pathways generating dysfunctional high-density lipoprotein. Antioxid Redox Signal 2012;8:1043–52.CrossrefWeb of ScienceGoogle Scholar

  • 34.

    Nigen AM, Njikam N, Lee CK, Manning JM. Studies on the mechanism of action of cyanate in sickle cell disease. Oxygen affinity and gelling properties of hemoglobin S carbamylated on specific chains. J Biol Chem 1974;249:6611–6.Google Scholar

  • 35.

    Harding JJ. Viewing molecular mechanisms of ageing through a lens. Ageing Res Rev 2002;1:465–79.Google Scholar

  • 36.

    Jaisson S, Lorimier S, Ricard-Blum S, Sockalingum GD, Delevallée-Forte C, Kegelaer G, et al. Impact of carbamylation on type I collagen conformational structure and its ability to activate human polymorphonuclear neutrophils. Chem Biol 2006;13:149–59.CrossrefPubMedGoogle Scholar

  • 37.

    Jaisson S, Larreta-Garde V, Bellon G, Hornebeck W, Garnotel R, Gillery P. Carbamylation differentially alters type I collagen sensitivity to various collagenases. Matrix Biol 2007;26: 190–6.Web of SciencePubMedCrossrefGoogle Scholar

  • 38.

    Garnotel R, Sabbah N, Jaisson S, Gillery P. Enhanced activation of and increased production of matrix metalloproteinase-9 by human blood monocytes upon adhering to carbamylated collagen. FEBS Lett 2004;563:13–6Google Scholar

  • 39.

    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 1999;133:302–8.Google Scholar

  • 40.

    Kraus LM, Gaber L, Handorf CR, Marti HP, Kraus AP Jr. Carbamoylation of glomerular and tubular proteins in patients with kidney failure: a potential mechanism of ongoing renal damage. Swiss Med Wkly 2001;131:139–45.Google Scholar

About the article

Corresponding author: Professor Philippe Gillery, MD, PhD, Laboratory of Pediatric Biology and Research, American Memorial Hospital, CHU of Reims, 47, Rue Cognacq-Jay, 51092 Reims cedex, France, Phone: +33 3 26783952, Fax: +33 3 26783882, E-mail:


Received: 2012-12-14

Accepted: 2013-02-04

Published Online: 2013-03-02

Published in Print: 2014-01-01


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 52, Issue 1, Pages 33–38, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0880.

Export Citation

©2014 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Ayse L. Mindikoglu, Antone R. Opekun, Nagireddy Putluri, Sridevi Devaraj, David Sheikh-Hamad, John M. Vierling, John A. Goss, Abbas Rana, Gagan K. Sood, Prasun K. Jalal, Lesley A. Inker, Robert P. Mohney, Hocine Tighiouart, Robert H. Christenson, Thomas C. Dowling, Matthew R. Weir, Stephen L. Seliger, William R. Hutson, Charles D. Howell, Jean-Pierre Raufman, Laurence S. Magder, and Cristian Coarfa
Translational Research, 2017
[2]
Manuela Aragno and Raffaella Mastrocola
Nutrients, 2017, Volume 9, Number 4, Page 385
[3]
Chhanda Bose, Sudhir V. Shah, Oleg K. Karaduta, Gur P. Kaushal, and Rajesh Mohanraj
PLOS ONE, 2016, Volume 11, Number 12, Page e0165576
[4]
Shankar Suman, Sanjay Mishra, and Yogeshwer Shukla
Expert Review of Proteomics, 2016, Volume 13, Number 12, Page 1073
[5]
Laëtitia Gorisse, Christine Pietrement, Vincent Vuiblet, Christian E. H. Schmelzer, Martin Köhler, Laurent Duca, Laurent Debelle, Paul Fornès, Stéphane Jaisson, and Philippe Gillery
Proceedings of the National Academy of Sciences, 2016, Volume 113, Number 5, Page 1191
[6]
Prathibha R. Gajjala, Danilo Fliser, Thimoteus Speer, Vera Jankowski, and Joachim Jankowski
Nephrology Dialysis Transplantation, 2015, Volume 30, Number 11, Page 1814
[7]
Philippe Gillery, Stéphane Jaisson, Laëtitia Gorisse, and Christine Pietrement
Néphrologie & Thérapeutique, 2015, Volume 11, Number 3, Page 129
[8]
P. Gillery
Annales Pharmaceutiques Françaises, 2014, Volume 72, Number 5, Page 330
[9]
Maarten B. Kok, Frans P.W. Tegelaers, Bastiaan van Dam, Jan L.M.L. van Rijn, and Johannes van Pelt
Clinica Chimica Acta, 2014, Volume 434, Page 6

Comments (0)

Please log in or register to comment.
Log in