Advanced glycation end products and the kidney

2005 ◽  
Vol 289 (4) ◽  
pp. F645-F659 ◽  
Author(s):  
Jürgen M. Bohlender ◽  
Sybille Franke ◽  
Günter Stein ◽  
Gunter Wolf
Keyword(s):  
Advanced Glycation End Products ◽  
Structural Changes ◽  
Therapeutic Potential ◽  
Interstitial Fibrosis ◽  
Basement Membranes ◽  
Renal Diseases ◽  
Advanced Glycation ◽  
Tubular Atrophy ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGEs) are a heterogeneous group of protein and lipids to which sugar residues are covalently bound. AGE formation is increased in situations with hyperglycemia (e.g., diabetes mellitus) and is also stimulated by oxidative stress, for example in uremia. It appears that activation of the renin-angiotensin system may contribute to AGE formation through various mechanisms. Although AGEs could nonspecifically bind to basement membranes and modify their properties, they also induce specific cellular responses including the release of profibrogenic and proinflammatory cytokines by interacting with the receptor for AGE (RAGE). However, additional receptors could bind AGEs, adding to the complexity of this system. The kidney is both: culprit and target of AGEs. A decrease in renal function increases circulating AGE concentrations by reduced clearance as well as increased formation. On the other hand, AGEs are involved in the structural changes of progressive nephropathies such as glomerulosclerosis, interstitial fibrosis, and tubular atrophy. These effects are most prominent in diabetic nephropathy, but they also contribute to renal pathophysiology in other nondiabetic renal diseases. Interference with AGE formation has therapeutic potential for preventing the progression of chronic renal diseases, as shown from data of animal experiments and, more recently, the first clinical trials.

scholarly journals Health Promoting Effect of Phyllanthus emblica and Azadiractha indica against Advanced Glycation End Products Formation

2021 ◽  
Vol 11 (19) ◽  
pp. 8819
Author(s):  
Mohammed A. Alsahli ◽  
Shehwaz Anwar ◽  
Faisal M. Alzahrani ◽  
Ahmad Almatroudi ◽  
Hani Alfheeaid ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Advanced Glycation End Products ◽  
Structural Changes ◽  
Therapeutic Potential ◽  
Health Problems ◽  
Phyllanthus Emblica ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Oxidative stress is linked with inflammation, diabetic complications, and advanced glycation end products formation. Intake of flavonoid-rich foods has been reported to have a beneficial effect on human health. The aim of this study was to verify the therapeutic potential of Phyllanthusemblica and Azadiractha indica against glycation and other oxidative stress-induced complications such as inflammation using in vitro study. Ethanol extracts of Phyllanthus emblica fruit pulp and dried leaf of Azadiractha indica were prepared to investigate in vitro anti-inflammatory and anti-glycating potentials. In a DPPH assay, the EC50 value of extract of P. emblica and A. indica was found to be 1532.36 ± 0.17 and 1380.61 ± 0.27 µg/mL, respectively. The FRAP value of P. emblica and A. indica extract was 86.6 and 32.12 µg ascorbic acid/100 mg dry weight of the extract. The maximum percentage of H2O2 scavenging activity was 71.30% and 67.38%, respectively. Extracts of P. emblica and A. indica showed maximum inhibition of heat-induced BSA denaturation by 62.42% and 53.00%, heat-induced denaturation of egg albumin, by 50.84%% and 44.31%, and heat-induced hemolysis by 54.44% and 50.21%. Both extracts (600 µg/mL) significantly reduced the browning, structural changes, aggregation, and AGEs formation. Our biophysical studies confirmed the AGEs formation was inhibiting the potential of extracts. Thus, our findings confirm that these extracts are a rich source of antioxidants and may be utilized to prevent the oxidative stress-induced destruction of biomolecules, glycation, and in the therapy of a variety of health problems, including inflammation. Further, a combination of extracts of P. emblica and A. indica may be extremely useful in preventing and treating health problems.

scholarly journals Ethyl Pyruvate Prevents Renal Damage Induced by Methylglyoxal-Derived Advanced Glycation End Products

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Eunsoo Jung ◽  
Wan Seok Kang ◽  
Kyuhyung Jo ◽  
Junghyun Kim
Keyword(s):  
Advanced Glycation End Products ◽  
Ethyl Pyruvate ◽  
Renal Diseases ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Cross Links

The renal accumulation of advanced glycation end products (AGEs) is a causative factor of various renal diseases, including chronic kidney disease and diabetic nephropathy. AGE inhibitors, such as aminoguanidine and pyridoxamine, have the therapeutic activities for reversing the increase in renal AGE burden. This study evaluated the inhibitory effects of ethyl pyruvate (EP) on methylglyoxal- (MGO-) modified AGE cross-links with proteins in vitro. We also determined the potential activity of EP in reducing the renal AGE burden in exogenously MGO-injected rats. EP inhibited MGO-modified AGE-bovine serum albumin (BSA) cross-links to collagen (IC50=0.19±0.03 mM) in a dose-dependent manner, and its activity was stronger than aminoguanidine (IC50=35.97±0.85 mM). In addition, EP directly trapped MGO (IC50=4.41±0.08 mM) in vitro. In exogenous MGO-injected rats, EP suppressed AGE burden and MGO-induced oxidative injury in renal tissues. These activities of EP on the MGO-mediated AGEs cross-links with protein in vitro and in vivo showed its pharmacological potential for inhibiting AGE-induced renal diseases.

scholarly journals A Breaker of Advanced Glycation End Products Attenuates Diabetes-Induced Myocardial Structural Changes

2003 ◽  
Vol 92 (7) ◽  
pp. 785-792 ◽  
Author(s):  
Riccardo Candido ◽  
Josephine M. Forbes ◽  
Merlin C. Thomas ◽  
Vicki Thallas ◽  
Rachael G. Dean ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Structural Changes ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Role of Dietary Advanced Glycation End Products in Diabetes Mellitus

2012 ◽  
Vol 18 (1) ◽  
pp. 50-66 ◽  
Author(s):  
Claudia Luevano-Contreras ◽  
Ma. Eugenia Garay-Sevilla ◽  
Karen Chapman-Novakofski
Keyword(s):  
Advanced Glycation End Products ◽  
Negative Impact ◽  
Cellular Level ◽  
Renal Diseases ◽  
Advanced Glycation ◽  
Cellular Mechanisms ◽  
Alternative Pathways ◽  
Glycation End Products ◽  
End Products

Dietary advanced glycation end products (AGEs) can be formed via the Maillard reaction and several alternative pathways. AGEs exert their deleterious effects by damaging protein structure and function, as well as through activation of cellular mechanisms. At the cellular level, the damaging effects of AGEs have been attributed to several AGE-binding proteins. Increased levels of AGEs have been implicated in several chronic diseases, including diabetes-related complications such as renal diseases, retinopathy, neuropathy, and cardiovascular diseases, as well as delayed wound healing. To investigate the role of AGEs thoroughly, a reliable assessment of dietary AGEs is needed. Varying methodology, diverse food preparation, and quantification of a variety of dietary AGEs makes this a complex goal. In addition, some antiglycation food products may balance or offset the negative impact of dietary AGEs.

scholarly journals Advanced glycation end products (AGEs), protein aggregation and their cross talk: new insight in tumorigenesis

Glycobiology ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 2-18
Author(s):  
Ejazul Haque ◽  
Mohd Kamil ◽  
Adria Hasan ◽  
Safia Irfan ◽  
Saba Sheikh ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Advanced Glycation End Products ◽  
Cross Talk ◽  
Structural Changes ◽  
Current Knowledge ◽  
Normal Function ◽  
Protein Glycation ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Abstract Protein glycation and protein aggregation are two distinct phenomena being observed in cancer cells as factors promoting cancer cell viability. Protein aggregation is an abnormal interaction between proteins caused as a result of structural changes in them after any mutation or environmental assault. Protein aggregation is usually associated with neurodegenerative diseases like Alzheimer’s and Parkinson’s, but of late, research findings have shown its association with the development of different cancers like lung, breast and ovarian cancer. On the contrary, protein glycation is a cascade of irreversible nonenzymatic reaction of reducing sugar with the amino group of the protein resulting in the modification of protein structure and formation of advanced glycation end products (AGEs). These AGEs are reported to obstruct the normal function of proteins. Lately, it has been reported that protein aggregation occurs as a result of AGEs. This aggregation of protein promotes the transformation of healthy cells to neoplasia leading to tumorigenesis. In this review, we underline the current knowledge of protein aggregation and glycation along with the cross talk between the two, which may eventually lead to the development of cancer.

scholarly journals Effect of dicarbonyl-induced browning on alpha-crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays

2004 ◽  
Vol 379 (2) ◽  
pp. 273-282 ◽  
Author(s):  
M. Satish KUMAR ◽  
P. Yadagiri REDDY ◽  
P. Anil KUMAR ◽  
Ira SUROLIA ◽  
G. Bhanuprakash REDDY
Keyword(s):  
Advanced Glycation End Products ◽  
Molecular Chaperone ◽  
Structural Changes ◽  
Surface Hydrophobicity ◽  
Enzyme Inactivation ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Enzymic Browning

α-Crystallin is a member of the small heat-shock protein family and functions like a molecular chaperone, and may thus help in maintaining the transparency of the eye lens by protecting the lens proteins from various stress conditions. Non-enzymic glycation of long-lived proteins has been implicated in several age- and diabetes-related complications, including cataract. Dicarbonyl compounds such as methylglyoxal and glyoxal have been identified as the predominant source for the formation of advanced glycation end-products in various tissues including the lens. We have investigated the effect of non-enzymic browning of α-crystallin by reactive dicarbonyls on its molecular chaperone-like function. Non-enzymic browning of bovine α-crystallin in vitro caused, along with altered secondary and tertiary structures, cross-linking and high-molecular-mass aggregation. Notwithstanding these structural changes, methylglyoxal- and glyoxal-modified α-crystallin showed enhanced anti-aggregation activity in various in vitro aggregation assays. Paradoxically, increased chaperone-like activity of modified α-crystallin was not associated with increased surface hydrophobicity and rather showed less 8-anilinonaphthalene-l-sulphonic acid binding. In contrast, the chaperone-like function of modified α-crystallin was found to be reduced in assays that monitor the prevention of enzyme inactivation by UV-B and heat. Moreover, incubation of bovine lens with methylglyoxal in organ culture resulted in cataract formation with accumulation of advanced glycation end-products and recovery of α-crystallin in high proportions in the insoluble fraction. Furthermore, soluble α-crystallin from methylglyoxal-treated lenses showed decreased chaperone-like activity. Thus, in addition to describing the effects of methylglyoxal and glyoxal on structure and chaperone-like activity, our studies also bring out an important caveat of aggregation assays in the context of the chaperone function of α-crystallin.

scholarly journals Expression of Advanced Glycation End Products and Their Cellular Receptor RAGE in Diabetic Nephropathy and Nondiabetic Renal Disease

2000 ◽  
Vol 11 (9) ◽  
pp. 1656-1666 ◽  
Author(s):  
NOZOMU TANJI ◽  
GLEN S. MARKOWITZ ◽  
CAIFENG FU ◽  
THOMAS KISLINGER ◽  
AKIHIKO TAGUCHI ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Lupus Nephritis ◽  
Focal Segmental Glomerulosclerosis ◽  
Advanced Glycation End Products ◽  
Basement Membranes ◽  
Advanced Glycation ◽  
Hypertensive Nephrosclerosis ◽  
Segmental Glomerulosclerosis ◽  
Glycation End Products ◽  
End Products

Abstract.Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms,i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n= 26), hypertensive nephrosclerosis (n= 7), idiopathic focal segmental glomerulosclerosis (n= 11), focal sclerosis secondary to obesity (n= 7), and lupus nephritis (n= 11) and from normal control subjects (n= 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE,i.e., Nϵ-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also identified in areas of glomerulosclerosis and arteriosclerosis in idiopathic and secondary focal segmental glomerulosclerosis, hypertensive nephrosclerosis, and lupus nephritis. In active lupus nephritis, CML and PENT were detected in the proliferative glomerular tufts and crescents. In conclusion, CML is a major AGE in renal basement membranes in diabetic nephropathy, and its accumulation involves upregulation of RAGE on podocytes. AGE are also accumulated in acute inflammatory glomerulonephritis secondary to systemic lupus erythematosus, possibly via enzymatic oxidation of glomerular matrix proteins.

Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy

2016 ◽  
Vol 7 (5-6) ◽  
pp. 293-309 ◽  
Author(s):  
Anil Kumar Pasupulati ◽  
P. Swathi Chitra ◽  
G. Bhanuprakash Reddy
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Basement Membranes ◽  
Renal Outcome ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Molecular Events ◽  
Glycation End Products ◽  
End Products

AbstractDiabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff’s base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.

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