scholarly journals Presence of dopa and amino acid hydroperoxides in proteins modified with advanced glycation end products (AGEs): amino acid oxidation products as a possible source of oxidative stress induced by AGE proteins

1998 ◽  
Vol 330 (1) ◽  
pp. 233-239 ◽  
Author(s):  
Shanlin FU ◽  
Min-Xin FU ◽  
W. John BAYNES ◽  
R. Suzanne THORPE ◽  
T. Roger DEAN
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Chemical Modification ◽  
Oxidation Products ◽  
Acid Oxidation ◽  
Advanced Glycation ◽  
Amino Acid Oxidation ◽  
Glycation End Products ◽  
End Products ◽  
Chemical Modification Of Proteins

Glycation and subsequent Maillard or browning reactions of glycated proteins, leading to the formation of advanced glycation end products (AGEs), are involved in the chemical modification of proteins during normal aging and have been implicated in the pathogenesis of diabetic complications. Oxidative conditions accelerate the browning of proteins by glucose, and AGE proteins also induce oxidative stress responses in cells bearing AGE receptors. These observations have led to the hypothesis that glycation-induced pathology results from a cycle of oxidative stress, increased chemical modification of proteins via the Maillard reaction, and further AGE-dependent oxidative stress. Here we show that the preparation of AGE-collagen by incubation with glucose under oxidative conditions in vitro leads not only to glycation and formation of the glycoxidation product Nε-(carboxymethyl)lysine (CML), but also to the formation of amino acid oxidation products on protein, including m-tyrosine, dityrosine, dopa, and valine and leucine hydroperoxides. The formation of both CML and amino acid oxidation products was prevented by anaerobic, anti-oxidative conditions. Amino acid oxidation products were also formed when glycated collagen, prepared under anti-oxidative conditions, was allowed to incubate under aerobic conditions that led to the formation of CML. These experiments demonstrate that amino acid oxidation products are formed in proteins during glycoxidation reactions and suggest that reactive oxygen species formed by redox cycling of dopa or by the metal-catalysed decomposition of amino acid hydroperoxides, rather than by redox activity or reactive oxygen production by AGEs on protein, might contribute to the induction of oxidative stress by AGE proteins.

scholarly journals Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B–RAGE-derived peptide complex

2015 ◽  
Vol 71 (5) ◽  
pp. 1176-1183 ◽  
Author(s):  
Jaime L. Jensen ◽  
Venkata S. K. Indurthi ◽  
David B. Neau ◽  
Stefan W. Vetter ◽  
Christopher L. Colbert
Keyword(s):  
Amino Acid ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Amino Acid Peptide ◽  
Extracellular Milieu ◽  
Amino Terminal ◽  
Binding Interface ◽  
Glycation End Products ◽  
End Products ◽  
Type V

S100B is a damage-associated molecular pattern protein that, when released into the extracellular milieu, triggers initiation of the inflammatory response through the receptor for advanced glycation end products (RAGE). Recognition of S100B is accomplishedviathe amino-terminal variable immunoglobulin domain (V-domain) of RAGE. To gain insights into this interaction, a complex between S100B and a 15-amino-acid peptide derived from residues 54–68 of the V-domain was crystallized. The X-ray crystal structure was solved to 2.55 Å resolution. There are two dimers of S100B and one peptide in the asymmetric unit. The binding interface of this peptide is compared with that found in the complex between S100B and the 12-amino-acid CapZ-derived peptide TRTK-12. This comparison reveals that although the peptides adopt completely different backbone structures, the residues buried at the interface interact with S100B in similar regions to form stable complexes. The binding affinities of S100B for the intact wild-type V-domain and a W61A V-domain mutant were determined to be 2.7 ± 0.5 and 1.3 ± 0.7 µM, respectively, using fluorescence titration experiments. These observations lead to a model whereby conformational flexibility in the RAGE receptor allows the adoption of a binding conformation for interaction with the stable hydrophobic groove on the surface of S100B.

scholarly journals Advanced Glycation End Products and Oxidative Stress in a Hyperglycaemic Environment

2021 ◽  
Author(s):  
Akio Nakamura ◽  
Ritsuko Kawahrada
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Advanced Glycation End Products ◽  
Reactive Oxygen ◽  
Protein Glycation ◽  
Oxygen Species ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Protein glycation is the random, nonenzymatic reaction of sugar and protein induced by diabetes and ageing; this process is quite different from glycosylation mediated by the enzymatic reactions catalysed by glycosyltransferases. Schiff bases form advanced glycation end products (AGEs) via intermediates, such as Amadori compounds. Although these AGEs form various molecular species, only a few of their structures have been determined. AGEs bind to different AGE receptors on the cell membrane and transmit signals to the cell. Signal transduction via the receptor of AGEs produces reactive oxygen species in cells, and oxidative stress is responsible for the onset of diabetic complications. This chapter introduces the molecular mechanisms of disease onset due to oxidative stress, including reactive oxygen species, caused by AGEs generated by protein glycation in a hyperglycaemic environment.

Citrus Fruit Extracts Reduce Advanced Glycation End Products (AGEs)- and H2O2-Induced Oxidative Stress in Human Adipocytes

2010 ◽  
Vol 58 (20) ◽  
pp. 11119-11129 ◽  
Author(s):  
Deena Ramful ◽  
Evelyne Tarnus ◽  
Philippe Rondeau ◽  
Christine Robert Da Silva ◽  
Theeshan Bahorun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Advanced Glycation End Products ◽  
Citrus Fruit ◽  
Human Adipocytes ◽  
Advanced Glycation ◽  
Fruit Extracts ◽  
Glycation End Products ◽  
End Products

Abstract 11598: Increased Advanced Glycation End-Products Accelerate the Progress of Left Ventricular Hypertrophy Under Condition of Elevated Oxidative Stress or Insulin Resistance in Patients With Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Aoyama Akihiro ◽  
Masuda Takashi ◽  
Ogura Misao ◽  
Shimizu Ryosuke ◽  
Kato Michitaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Clinical Characteristics ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
One Year ◽  
Observation Period

Background: Elevated oxidative stress or insulin resistance has been shown to promote the production of advanced glycation end-products (AGEs) in patients with hypertension (HT). Because AGEs enhance left ventricular hypertrophy (LVH) via the activation of nuclear factor-kappa B, it is considered that increased AGEs contribute to LVH in HT patients. The aim of this study was to investigate the effect of increased AGEs on LVH in them. Methods: Eighty five HT patients aged 65 ± 9 years were prospectively followed up for a year, whose blood pressure was controlled under 140/90mmHg. We assessed patients’ glucose and lipid metabolism and neurohumoral factors including plasma noradrenaline and renin activity as clinical characteristics. We measured serum malondialdehyde-modified LDL-cholesterol (MDA-LDL) and plasma pentosidine as parameters of oxidative stress and AGEs, respectively. Homeostasis model assessment ratio (HOMA-R), estimate glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) were assessed as parameters of insulin resistance, renal function and LVH, respectively. All parameters were assessed before and after one-year observation period. We examined the change in each parameter from baseline to the value measured after the observation period ([[Unable to Display Character: &#8895;]]MDA-LDL, [[Unable to Display Character: &#8895;]]pentosidine, [[Unable to Display Character: &#8895;]]HOMA-R and [[Unable to Display Character: &#8895;]]LVMI). We divided patients into two groups based on the median of baseline pentosidine: high AGEs and low AGEs groups. We compared baseline values between the two groups. We analyzed the relationships among [[Unable to Display Character: &#8895;]]MDA-LDL, [[Unable to Display Character: &#8895;]]HOMA-R, [[Unable to Display Character: &#8895;]]Pentosidine and [[Unable to Display Character: &#8895;]]LVMI, and performed stepwise multiple regression analysis using parameters of clinical characteristics and AGEs to detect the predictors for the LVH progress after one year. Results: Baseline LVMI was significantly higher in the high AGEs group than in the low AGEs group (P<0.05). [[Unable to Display Character: &#8895;]]Pentosidine was positively correlated with [[Unable to Display Character: &#8895;]]MDA-LDL (r=0.34, P<0.01),[[Unable to Display Character: &#8895;]]HOMA-R (r=0.37, P<0.01) and [[Unable to Display Character: &#8895;]]LVMI (r=0.39, P<0.05). Multiple regression analysis detected pentosidine as a significant independent predictor for the LVH progress (β=0.407, P=0.005) (R2=0.315). Conclusion: Increased AGEs accelerated the LVH progress under condition of elevated oxidative stress or insulin resistance in HT patients.

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