scholarly journals N ε-(Carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins

1997 ◽  
Vol 324 (2) ◽  
pp. 565-570 ◽  
Author(s):  
Mahtab U. AHMED ◽  
Elisabeth BRINKMANN FRYE ◽  
Thorsten P. DEGENHARDT ◽  
Suzanne R. THORPE ◽  
John W. BAYNES
Keyword(s):  
Advanced Glycation End Products ◽  
Human Lens ◽  
Advanced Glycation ◽  
Model Compounds ◽  
Lens Proteins ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues ◽  
Carboxymethyl Lysine ◽  
Chemical Modification Of Proteins

Advanced glycation end-products and glycoxidation products, such as Nϵ-(carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue proteins with age and are implicated in the aging of tissue proteins and in the development of pathology in diabetes, atherosclerosis and other diseases. In this paper we describe a new advanced glycation end-product, Nϵ-(carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal with lysine residues in model compounds and in the proteins RNase and collagen. CEL was also detected in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Although CEL was formed in highest yields during the reaction of methylglyoxal and triose phosphates with lysine and protein, it was also formed in reactions of pentoses, ascorbate and other sugars with lysine and RNase. We propose that levels of CML and CEL and their ratio to one another in tissue proteins and in urine will provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease.

Methylglyoxal-Derived Hydroimidazolone Advanced Glycation End-Products of Human Lens Proteins

2003 ◽  
Vol 44 (12) ◽  
pp. 5287 ◽  
Author(s):  
Naila Ahmed ◽  
Paul J. Thornalley ◽  
Jens Dawczynski ◽  
Sybille Franke ◽  
Juergen Strobel ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Human Lens ◽  
Advanced Glycation ◽  
Lens Proteins ◽  
Glycation End Products ◽  
End Products

Advanced glycation end-products associate with podocytopathy in type II diabetic patients

2021 ◽  
Author(s):  
Rajkishor Nishad ◽  
Tahaseen V Syed ◽  
Manga Motrapu ◽  
Rajesh Kavvuri ◽  
Kiranmayi Kodali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Type Ii ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine

Abstract Background The prevalence of diabetes reaches epidemic proportions, affecting the incidence of diabetic nephropathy (DN) and associated end-stage kidney disease (ESKD). Diabetes is the leading cause of ESKD since 30–40% of diabetic patients develop DN. Albuminuria and eGFR have been considered a surrogate outcome of chronic kidney disease, and the search for a biomarker that predicts progression to diabetic kidney disease is intense.Methods We analyzed the association of serum advanced glycation end-products (AGEs) index (AGI) with impaired kidney function in uncontrolled diabetic patients (type II, n = 130) with albuminuria ranging from (150 to 450 mg/day). The kidney biopsy specimens were also examined for the association of AGEs, particularly carboxymethyl lysine (CML) with kidney function. Further, we also assessed the effect of carboxymethyl lysine on glomerular injury and podocytopathy in experimental animals.Results We observed a strong correlation between AGI and impaired kidney function in miroalbuminuric patients with hyperglycemia. A significant association between CML levels and impaired kidney function was noticed. Administration of CML in mice showed heavy proteinuria and glomerular abnormalities. Reduced podocyte number observed in mice administered with CML could be attributed to the epithelial-mesenchymal transition (EMT) of podocytes. Conclusion Serum AGEs could be independently related to the podocyte injury vis-a-vis the risk of DN progression to ESKD in patients with microalbuminuria. AGEs or CML could be considered a prognostic marker to assess microalbuminuria progression to ESKD in diabetic patients.

scholarly journals Advanced Glycation End Products: Formation, Role in Diabetic Complications, and Potential in Clinical Applications

2020 ◽  
Author(s):  
Rujman Khan ◽  
Xin Yee Ooi ◽  
Matthew Parvus ◽  
Laura Valdez ◽  
Andrew Tsin
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Diabetic Complications ◽  
Tanshinone Iia ◽  
Future Research ◽  
Advanced Glycation ◽  
Reactive Aldehydes ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.

Accumulation of fructosyl-lysine and advanced glycation end products in the kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats

2003 ◽  
Vol 31 (6) ◽  
pp. 1423-1425 ◽  
Author(s):  
N. Karachalias ◽  
R. Babaei-Jadidi ◽  
N. Ahmed ◽  
P.J. Thornalley
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Plasma Protein ◽  
Advanced Glycation End Products ◽  
Diabetic Rats ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine

The accumulation of AGEs (advanced glycation end products) in diabetes mellitus has been implicated in the biochemical dysfunction associated with the chronic development of microvascular complications of diabetes – nephropathy, retinopathy and peripheral neuropathy. We investigated the concentrations of fructosyl-lysine and AGE residues in protein extracts of renal glomeruli, retina, peripheral nerve and plasma protein of streptozotocin-induced diabetic rats and normal healthy controls. Glycation adducts were determined by LC with tandem MS detection. In diabetic rats, the fructosyl-lysine concentration was increased markedly in glomeruli, retina, sciatic nerve and plasma protein. The concentrations of N∊-carboxymethyl-lysine and N∊-carboxyethyl-lysine were increased in glomeruli, sciatic nerve and plasma protein, and N∊-carboxymethyl-lysine also in the retina. Hydroimidazolone AGEs derived from glyoxal, methylglyoxal and 3-deoxylglucosone were major AGEs quantitatively. They were increased in the retina, nerve, glomeruli and plasma protein. AGE accumulation in renal glomeruli, retina, peripheral nerve and plasma proteins is consistent with a role for AGEs in the development of nephropathy, retinopathy and peripheral neuropathy in diabetes. High-dose therapy with thiamine and Benfotiamine suppressed the accumulation of AGEs, and is a novel approach to preventing the development of diabetic complications.

scholarly journals Effects of photobleaching on selected advanced glycation end products in the human lens

2015 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Thomas Holm ◽  
Cibin T Raghavan ◽  
Rooban Nahomi ◽  
Ram H Nagaraj ◽  
Line Kessel
Keyword(s):  
Advanced Glycation End Products ◽  
Human Lens ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals Leptin and advanced glycation end products receptor (RAGE) in tuberculosis patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254198
Author(s):  
Tássia Kirchmann Lazzari ◽  
Erika Cavalheiro ◽  
Sandra Eugênia Coutinho ◽  
Lívia Fontes da Silva ◽  
Denise Rossato Silva
Keyword(s):  
Weight Loss ◽  
Advanced Glycation End Products ◽  
Inverse Correlation ◽  
Advanced Glycation ◽  
Serum Leptin ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine ◽  
Control Study

Introduction The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host’s inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE. Methods Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA. Results We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48–14.11] ng/mL vs 3.08 [0.54–6.34] ng/mL; p = 0.028). Conclusions We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings.

scholarly journals Effect of thioltransferase on oxidative stress induced by high glucose and advanced glycation end products in human lens epithelial cells

2021 ◽  
Vol 14 (7) ◽  
pp. 965-972
Author(s):  
Qing Liu ◽  
◽  
Hong Yan ◽  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
High Glucose ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Advanced Glycation ◽  
Human Lens Epithelial Cells ◽  
Glycation End Products ◽  
End Products

AIM: To study the effect of thioltransferase (TTase) on oxidative stress in human lens epithelial cells (HLECs) induced by high glucose and advanced glycation end products (AGEs). METHODS: HLECs were treated with 35.5 mmol/L glucose or 1.5 mg/mL AGEs modified bovine serum albumin (AGEs-BSA) as the experimental groups, respectively. Cells were collected at the time point of 1, 2, 3, and 4d. The TTase activity were measured accordingly. TTase mRNA levels were detected by quantitative reverse transcription polymerase chain response (qRT-RCR) and its protein level was detected by Western blot. The siRNA was used to knock down the expression of TTase. The activity of catalase (CAT) and superoxide dismutase (SOD), the content of reactive oxygen species (ROS) and the ratio of oxidized glutathione/total glutathione (GSSG/T-GSH) were assessed in different groups, respectively. RESULTS: The level of TTase mRNA gradually increased and reached the top at 2d, then it decreased to the normal level at 4d, and the TTase activity increased from 2 to 3d in both high glucose and AGEs-BSA groups. The TTase expression elevated from 2d in high glucose group, and it began to rise from 3d in AGEs-BSA group. The activity of CAT and SOD showed a decrease and the content of ROS and the ratio of GSSG/T-GSH showed an increase in high glucose and AGEs-BSA group. These biochemical alterations were more prominent in the groups with TTase siRNA. CONCLUSION: High glucose and AGEs can increase ROS content in HLECs; therefore, it induces oxidative stress. This may result in the decreased GSH and increased GSSG content, impaired activity of SOD and CAT. The up-regulated TTase likely provides oxidation damage repair induced by high glucose and AGEs in the early stage.

scholarly journals Glyceraldehyde-Derived Advanced Glycation End Products Accumulate Faster Than Nε-(Carboxymethyl) Lysine

2017 ◽  
Vol 29 (4) ◽  
pp. 508
Author(s):  
Mami Yokota ◽  
Marie Sekita ◽  
Yuri Okano ◽  
Hitoshi Masaki ◽  
Masayoshi Takeuchi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine
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