scholarly journals Nε-(Carboxymethyl)Lysine Adducts of Proteins Are Ligands for Receptor for Advanced Glycation End Products That Activate Cell Signaling Pathways and Modulate Gene Expression

1999 ◽  
Vol 274 (44) ◽  
pp. 31740-31749 ◽  
Author(s):  
Thomas Kislinger ◽  
Caifeng Fu ◽  
Birgit Huber ◽  
Wu Qu ◽  
Akihiko Taguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine ◽  
Activate Cell ◽  
Cell Signaling Pathways

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.

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 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.

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 Advanced Glycation End Products of Bovine Serum Albumin Suppressed Th1/Th2 Cytokine but Enhanced Monocyte IL-6 Gene Expression via MAPK-ERK and MyD88 Transduced NF-κB p50 Signaling Pathways

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2461 ◽  
Author(s):  
Chieh-Yu Shen ◽  
Cheng-Han Wu ◽  
Cheng-Hsun Lu ◽  
Yu-Min Kuo ◽  
Ko-Jen Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Advanced Glycation End Products ◽  
Binding Capacity ◽  
Carboxypeptidase Y ◽  
Functional Assay ◽  
Low Grade ◽  
Conformational Structure ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGE), the most known aging biomarker, may cause “inflamm-aging” (i.e., chronic low-grade inflammation that develops with aging) in both aged and diabetes groups. However, the molecular bases of inflamm-aging remain obscure. We prepared AGE by incubating BSA (0.0746 mmol/L) + glucose (0.5 mol/L) at 37 °C in 5% CO2–95% air for 1–180 days. The lysine glycation in BSA–AGE reached 77% on day 30 and 100% after day 130, whereas the glycation of arginine and cysteine was minimal. The Nε-(carboxymethyl)-lysine content in BSA–AGE was also increased with increasing number of incubation days. The lectin-binding assay revealed that the glycation of BSA not only altered the conformational structure, but lost binding capacity with various lectins. An immunological functional assay showed that BSA–AGE > 8 μg/mL significantly suppressed normal human Th1 (IL-2 and IFN-γ) and Th2 (IL-10) mRNA expression, whereas AGE > 0.5 μg/mL enhanced monocyte IL-6 production irrelevant to cell apoptosis. The AGE-enhanced monocyte IL-6 production was via MAPK–ERK and MyD88-transduced NF-κBp50 signaling pathways. To elucidate the structure–function relationship of BSA–AGE-enhanced IL-6 production, we pre-preincubated BSA–AGE with different carbohydrate-degrading, protein-degrading, and glycoprotein-degrading enzymes. We found that trypsin and carboxypeptidase Y suppressed whereas β-galactosidase enhanced monocyte IL-6 production. In conclusion, BSA–AGE exerted both immunosuppressive and pro-inflammatory effects that are the molecular basis of inflamm-aging in aged and diabetes groups.

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