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Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells

  • Christos Adamopoulos , Elena Farmaki , Eliana Spilioti , Hippokratis Kiaris , Christina Piperi EMAIL logo and Athanasios G. Papavassiliou
Published/Copyright: March 2, 2013
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 52 Issue 1

Abstract

Background: Advanced glycation end products (AGEs), the final products of the Maillard reaction, have been shown to impair endothelial proliferation and function, thus contributing to endothelial cell injury present in diabetes, inflammatory and cardiovascular diseases. Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic and oxidative conditions has been implicated in endothelial dysfunction through activation of the unfolded protein response (UPR). The present study investigates the role of AGEs in ER stress induction in human aortic endothelial cells exposed to variable AGE treatments.

Methods: Human aortic endothelial cells (HAEC) were treated with increasing concentrations (100, 200 μg/mL) of AGE-bovine serum albumin (AGE-BSA) at different time-points (24, 48, 72 h). The induction of ER stress and the involved UPR components were investigated on mRNA and protein levels. Apoptosis was quantitatively determined by flow cytometry detecting propidium iodide expression and annexin V binding simultaneously.

Results: AGEs administration significantly reduced HAEC proliferation in a time- and dose-dependent manner. An immediate induction of the ER chaperones GRP78, GRP94 and the transcriptional activator, XBP-1 was observed at 24 h and 48 h. A later induction of the phospho-elF2α and proapoptotic transcription factor CHOP was observed at 48 h and 72 h, being correlated with elevated early apoptotic cell numbers at the same time-points.

Conclusions: The present study demonstrates that AGEs directly induce ER stress in human aortic endothelial cells, playing an important role in endothelial cell apoptosis. Targeting AGEs signaling pathways in order to alleviate ER stress may prove of therapeutic potential to endothelial dysfunction-related disorders.

Keywords: advanced glycation end-products (AGEs); apoptosis; endoplasmic reticulum (ER) stress; human aortic endothelial cells; unfolded protein response (UPR)
Corresponding author: Assistant Professor Christina Piperi, PhD, Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, 11527 Athens, Greece, Phone: +30 210 7462610, Fax: +30 210 8037372, E-mail:

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Received: 2012-11-29
Accepted: 2013-2-7
Published Online: 2013-03-02
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-2012-0826
Keywords for this article
advanced glycation end-products (AGEs); apoptosis; endoplasmic reticulum (ER) stress; human aortic endothelial cells; unfolded protein response (UPR)

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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