scholarly journals Advanced glycation end products cause RAGE ‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models

JOR Spine ◽  
2020 ◽  
Vol 3 (4) ◽  
Author(s):  
Robert C. Hoy ◽  
Danielle N. D'Erminio ◽  
Divya Krishnamoorthy ◽  
Devorah M. Natelson ◽  
Damien M. Laudier ◽  
...  
Keyword(s):  
Annulus Fibrosus ◽  
Second Harmonic ◽  
Intervertebral Disk ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Culture Models ◽  
Second Harmonic Generation Imaging

scholarly journals Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 453
Author(s):  
Ana Filošević Vujnović ◽  
Katarina Jović ◽  
Emanuel Pištan ◽  
Rozi Andretić Waldowski
Keyword(s):  
Drosophila Melanogaster ◽  
Advanced Glycation End Products ◽  
Model Organism ◽  
Covalent Modification ◽  
Advanced Glycation ◽  
Biomarkers Of Aging ◽  
Glycation End Products ◽  
End Products

Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

Dietary sugars and related endogenous advanced glycation end-products increase chromosomal DNA damage in WIL2-NS cells, measured using cytokinesis-block micronucleus cytome assay

Mutagenesis ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Permal Deo ◽  
Caitlin L McCullough ◽  
Theodora Almond ◽  
Emma L Jaunay ◽  
Leigh Donnellan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Advanced Glycation End Products ◽  
Chromosomal Dna ◽  
Advanced Glycation ◽  
Age Related ◽  
Genome Damage ◽  
Glycation End Products ◽  
End Products ◽  
High Concentrations

Abstract This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu–BSA) or with fructose (Fru–BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML; 26.76 ± 1.09 nmol/mg BSA) levels in the Glu–BSA model. Nε-Carboxyethyllysine (CEL; 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1; 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru–BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu–BSA or Fru–BSA. Fructose treatment exerted a significant genotoxic dose–response effect including increases of BN with MNi (R2 = 0.7704; P = 0.0031), BN with NPBs (R2 = 0.9311; P < 0.0001) and BN with NBuds (R2 = 0.7118; P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400–600 µg/ml) induced DNA damage; however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo.

scholarly journals Use of Grape Pomace Phenolics to Counteract Endogenous and Exogenous Formation of Advanced Glycation End-Products

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1917 ◽  
Author(s):  
Pedapati S. C. Sri Harsha ◽  
Vera Lavelli
Keyword(s):  
Advanced Glycation End Products ◽  
Grape Pomace ◽  
Advanced Glycation ◽  
Sweetened Beverages ◽  
Glycation End Products ◽  
End Products ◽  
Food Applications ◽  
Double Blinded

The increase in consumption of “ultra-processed” foods has raised attention because of the possible adverse effects deriving from the Maillard reaction leading to the formation of toxic advanced glycation end-products (AGEs) during food processing. Additionally, the increasing trend and consumption of sugar-added foods and sweetened beverages is related to the endogenous formation of the same toxic compounds. However, ultra-processing in the context of food technology can bring challenges as well as a wealth of opportunities. Indeed, re-processing of grape pomace, a by-product of winemaking, can yield phenolic-rich fractions that efficiently counteract the effects of AGEs. In this review, the process of endogenous and exogenous AGE formation is illustrated. Then, the ability of grape phenolics to act as inhibitors of AGE formation is presented, including the efficacy ranking of various individual compounds measured in vitro and the outcome of in vivo double-blinded randomized crossover trials designed to prove the efficacy of grape phenolics as inhibitors of protein carbonylation. Finally, a survey of model functional foods added with grape phenolics, either to lower the dietary load of AGEs or to deliver antiglycation agents in vivo is listed in order to highlight the opportunity to develop safe and tailor-made “anti-AGEs” food applications.

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 Proteolytic release of the receptor for advanced glycation end products from in vitro and in situ alveolar epithelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. L516-L525 ◽  
Author(s):  
Naoko Yamakawa ◽  
Tokujiro Uchida ◽  
Michael A. Matthay ◽  
Koshi Makita
Keyword(s):  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Alveolar Epithelial Cells ◽  
Advanced Glycation ◽  
Alveolar Epithelial ◽  
Lps Challenge ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Although the receptor for advanced glycation end products (RAGE) has been used as a biological marker of alveolar epithelial cell injury in clinical studies, the mechanism for release of soluble RAGE from lung epithelial cells has not been well studied. Therefore, these studies were designed to determine the mechanism for release of soluble RAGE after lipopolysaccharide (LPS) challenge. For these purposes, alveolar epithelial cells from rat lungs were cultured on Transwell inserts, and LPS was added to the apical side (500 μg/ml) for 16 h on day 7. On day 7, RAGE was expressed predominantly in surfactant protein D-negative cells, and LPS challenge induced release of RAGE into the medium. This response was partially blocked by matrix metalloproteinase (MMP) inhibitors. Transcripts of MMP-3 and MMP-13 were upregulated by LPS, whereas RAGE transcripts did not change. Proteolysis by MMP-3 and MMP-13 resulted in soluble RAGE expression in the bronchoalveolar lavage fluid in the in situ rat lung, and this reaction was inhibited by MMP inhibitors. In human studies, both MMP-3 and -13 antigen levels were significantly correlated with the level of RAGE in pulmonary edema fluid samples. These results support the conclusion that release of RAGE is primarily mediated by proteolytic damage in alveolar epithelial cells in the lung, caused by proteases in acute inflammatory conditions in the distal air spaces.

scholarly journals Diabetic threesome (hyperglycaemia, renal function and nutrition) and advanced glycation end products: evidence for the multiple-hit agent?

2008 ◽  
Vol 67 (1) ◽  
pp. 60-74 ◽  
Author(s):  
Kateřina Kaňková
Keyword(s):  
Advanced Glycation End Products ◽  
Biological Properties ◽  
Advanced Glycation ◽  
Similar Chemical ◽  
Wide Range ◽  
Glycation End Products ◽  
End Products ◽  
Genes Encoding ◽  
Sugar Derivatives

Complex chemical processes termed non-enzymic glycation that operate in vivo and similar chemical interactions between sugars and proteins that occur during thermal processing of food (known as the Maillard reaction) are one of the interesting examples of a potentially-harmful interaction between nutrition and disease. Non-enzymic glycation comprises a series of reactions between sugars, α-oxoaldehydes and other sugar derivatives and amino groups of amino acids, peptides and proteins leading to the formation of heterogeneous moieties collectively termed advanced glycation end products (AGE). AGE possess a wide range of chemical and biological properties and play a role in diabetes-related pathology as well as in several other diseases. Diabetes is, nevertheless, of particular interest for several reasons: (1) chronic hyperglycaemia provides the substrates for extracellular glycation as well as intracellular glycation; (2) hyperglycaemia-induced oxidative stress accelerates AGE formation in the process of glycoxidation; (3) AGE-modified proteins are subject to rapid intracellular proteolytic degradation releasing free AGE adducts into the circulation where they can bind to several pro-inflammatory receptors, especially receptor of AGE; (4) kidneys, which are principally involved in the excretion of free AGE adducts, might be damaged by diabetic nephropathy, which further enhances AGE toxicity because of diminished AGE clearance. Increased dietary intake of AGE in highly-processed foods may represent an additional exogenous metabolic burden in addition to AGE already present endogenously in subjects with diabetes. Finally, inter-individual genetic and functional variability in genes encoding enzymes and receptors involved in either the formation or the degradation of AGE could have important pathogenic, nutrigenomic and nutrigenetic consequences.

scholarly journals Advanced glycation end products promote hepatosteatosis by interfering with SCAP-SREBP pathway in fructose-drinking mice

2013 ◽  
Vol 305 (6) ◽  
pp. G398-G407 ◽  
Author(s):  
Raffaella Mastrocola ◽  
Massimo Collino ◽  
Mara Rogazzo ◽  
Claudio Medana ◽  
Debora Nigro ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
De Novo ◽  
Regulatory Element ◽  
Plasma Lipid ◽  
De Novo Lipogenesis ◽  
Advanced Glycation ◽  
Sugary Drinks ◽  
Glycation End Products ◽  
End Products

Clinical studies have linked the increased consumption of fructose to the development of obesity, dyslipidemia, and impaired glucose tolerance, and a role in hepatosteatosis development is presumed. Fructose can undergo a nonenzymatic reaction from which advanced glycation end products (AGEs) are derived, leading to the formation of dysfunctional, fructosylated proteins; however, the in vivo formation of AGEs from fructose is still less known than that from glucose. In the present study C57Bl/6J mice received 15% (wt/vol) fructose (FRT) or 15% (wt/vol) glucose (GLC) in water to drink for 30 wk, resembling human habit to consume sugary drinks. At the end of the protocol both FRT- and GLC-drinking mice had increased fasting glycemia, glucose intolerance, altered plasma lipid profile, and marked hepatosteatosis. FRT mice had higher hepatic triglycerides deposition than GLC, paralleled by a greater increased expression and activity of the sterol regulatory element-binding protein 1 (SREBP1), the transcription factor responsible for the de novo lipogenesis, and of its activating protein SCAP. LC-MS analysis showed a different pattern of AGE production in liver tissue between FRT and GLC mice, with larger amount of carboxymethyl lysine (CML) generated by fructose. Double immunofluorescence and coimmunoprecipitation analysis revealed an interaction between CML and SCAP that could lead to prolonged activation of SREBP1. Overall, the high levels of CML and activation of SCAP/SREBP pathway associated to high fructose exposure here reported may suggest a key role of this signaling pathway in mediating fructose-induced lipogenesis.

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