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Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes

  • Paul Voziyan EMAIL logo , Kyle L. Brown , Sergei Chetyrkin and Billy Hudson
Published/Copyright: March 13, 2013
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 52 Issue 1

Abstract

Non-enzymatic modification of proteins in hyperglycemia is a major proposed mechanism of diabetic complications. Specifically, advanced glycation end products (AGEs) derived from hyperglycemia-induced reactive carbonyl species (RCS) can have pathogenic consequences when they target functionally critical protein residues. Modification of a small number of these critical residues, often undetectable by the methodologies relying on measurements of total AGE levels, can cause significant functional damage. Therefore, detection of specific sites of protein damage in diabetes is central to understanding the molecular basis of diabetic complications and for identification of biomarkers which are mechanistically linked to the disease. The current paradigm of RCS-derived protein damage places a major focus on methylglyoxal (MGO), an intermediate of cellular glycolysis. We propose that glyoxal (GO) is a major contributor to extracellular matrix (ECM) damage in diabetes. Here, we review the current knowledge and provide new data about GO-derived site-specific ECM modification in experimental diabetes.

Keywords: advanced glycation end products; collagen IV; diabetes; extracellular matrix; glyoxal; mass spectrometry; methylglyoxal; pyridoxamine
Corresponding author: Dr. Paul Voziyan, Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, S-3223 MCN, 1161 21st Avenue South, Nashville, TN 37232–2372, USA, Phone: +1-615-322-3352, Fax: +1-615-343-7156, E-mail:

This work was supported by grant DK65138 from the National Institutes of Health.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2012-11-27
Accepted: 2013-2-7
Published Online: 2013-03-13
Published in Print: 2014-01-01

©2014 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Editorial
  4. Frontiers in research on the Maillard reaction in aging and chronic disease
  5. Reviews
  6. Role of the Maillard reaction in aging and age-related diseases. Studies at the cellular-molecular level
  7. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review
  8. Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications
  9. Mini Reviews
  10. Post-translational modification derived products (PTMDPs): toxins in chronic diseases?
  11. Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes
  12. Augmentation of blood lipid glycation and lipid oxidation in diabetic patients
  13. Maillard reaction products: some considerations on their health effects
  14. The Maillard reaction and food allergies: is there a link?
  15. Perspectives
  16. Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma
  17. Genetics and Molecular Diagnostics
  18. Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality
  19. General Clinical Chemistry and Laboratory Medicine
  20. Quantification of glyoxal, methylglyoxal and 3-deoxyglucosone in blood and plasma by ultra performance liquid chromatography tandem mass spectrometry: evaluation of blood specimen
  21. A new HPLC-based assay for the measurement of fructosamine-3-kinase (FN3K) and FN3K-related protein activity in human erythrocytes
  22. Increased circulating advanced glycation endproducts (AGEs) in acute trauma patients
  23. Circulating soluble RAGE increase after a cerebrovascular event
  24. Pentosidine determination in CSF: a potential biomarker of Alzheimer’s disease?
  25. Cardiovascular Diseases
  26. Skin autofluorescence as proxy of tissue AGE accumulation is dissociated from SCORE cardiovascular risk score, and remains so after 3 years
  27. Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure
  28. Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects
  29. Translational Research Papers
  30. Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells
  31. Formation of nitri- and nitrosylhemoglobin in systems modeling the Maillard reaction
  32. Skin aging by glycation: lessons from the reconstructed skin model
  33. How to help the skin cope with glycoxidation
https://doi.org/10.1515/cclm-2012-0818
Keywords for this article
advanced glycation end products; collagen IV; diabetes; extracellular matrix; glyoxal; mass spectrometry; methylglyoxal; pyridoxamine

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Editorial
  4. Frontiers in research on the Maillard reaction in aging and chronic disease
  5. Reviews
  6. Role of the Maillard reaction in aging and age-related diseases. Studies at the cellular-molecular level
  7. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review
  8. Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications
  9. Mini Reviews
  10. Post-translational modification derived products (PTMDPs): toxins in chronic diseases?
  11. Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes
  12. Augmentation of blood lipid glycation and lipid oxidation in diabetic patients
  13. Maillard reaction products: some considerations on their health effects
  14. The Maillard reaction and food allergies: is there a link?
  15. Perspectives
  16. Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma
  17. Genetics and Molecular Diagnostics
  18. Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality
  19. General Clinical Chemistry and Laboratory Medicine
  20. Quantification of glyoxal, methylglyoxal and 3-deoxyglucosone in blood and plasma by ultra performance liquid chromatography tandem mass spectrometry: evaluation of blood specimen
  21. A new HPLC-based assay for the measurement of fructosamine-3-kinase (FN3K) and FN3K-related protein activity in human erythrocytes
  22. Increased circulating advanced glycation endproducts (AGEs) in acute trauma patients
  23. Circulating soluble RAGE increase after a cerebrovascular event
  24. Pentosidine determination in CSF: a potential biomarker of Alzheimer’s disease?
  25. Cardiovascular Diseases
  26. Skin autofluorescence as proxy of tissue AGE accumulation is dissociated from SCORE cardiovascular risk score, and remains so after 3 years
  27. Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure
  28. Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects
  29. Translational Research Papers
  30. Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells
  31. Formation of nitri- and nitrosylhemoglobin in systems modeling the Maillard reaction
  32. Skin aging by glycation: lessons from the reconstructed skin model
  33. How to help the skin cope with glycoxidation
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