Generation and characterization of monoclonal antibody against Advanced Glycation End Products in chronic kidney disease

Finco, Alessandra Becker; Machado-de-Ávila, Ricardo Andrez; Maciel, Rayana Ariane Pereira; Moura, Juliana de; Billiald, Philippe; Stinghen, Andréa Emília Marques; Alvarenga, Larissa M.

doi:10.1016/j.bbrep.2016.03.011

Cited by 6 publications

(7 citation statements)

References 29 publications

(26 reference statements)

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“…Advanced glycation end products (AGEs), proinflammatory and pro-oxidative compounds classified as uremic toxins, are produced through the non-enzymatic glycation and oxidation of proteins, lipids, and nucleic acids. Their accumulation in CKD promotes endothelial dysfunction and subsequent diseases [ 115 , 116 , 117 , 118 , 119 , 120 ]. Atherosclerosis, autoimmune disease, diabetes mellitus, and inflammatory diseases are closely linked to the AGE receptor-ligand axis [ 121 , 122 , 123 , 124 ].…”

Section: Transporters and Receptors Of Uremic Toxins In The Endothmentioning

confidence: 99%

How do Uremic Toxins Affect the Endothelium?

Cunha

Santos

Barreto

et al. 2020

Toxins

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Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, such as transporters and receptors, can mediate the interaction between uremic toxins and endothelial cells. In these cells, uremic toxins induce oxidative stress and activation of signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways leads to overexpression of proinflammatory (e.g., monocyte chemoattractant protein-1, E-selectin) and prothrombotic (e.g., tissue factor) proteins. Uremic toxins also induce the formation of endothelial microparticles (EMPs), which can lead to the activation and dysfunction of other cells, and modulate the expression of microRNAs that have an important role in the regulation of cellular processes. The resulting endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases, such as atherosclerosis and thrombotic events. Therefore, uremic toxins as well as the pathways they modulated may be potential targets for therapies in order to improve treatment for patients with CKD.

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Section: Transporters and Receptors Of Uremic Toxins In The Endothmentioning

confidence: 99%

How do Uremic Toxins Affect the Endothelium?

Cunha

Santos

Barreto

et al. 2020

Toxins

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show abstract

“…However, methods based on the detection of autofluorescence of AGEs are limited as they exclusively measure the total fluorescent glycation. New promising methodologies for high-throughput generation of monoclonal antibodies mapped with epitopes against AGE have been applied and validated [26,27]. Signs of progress have been obtained in identifying epitopes, reaching a high level of sensitivity and a simple analytical procedure [26,27].…”

Section: Introductionmentioning

confidence: 99%

“…New promising methodologies for high-throughput generation of monoclonal antibodies mapped with epitopes against AGE have been applied and validated [26,27]. Signs of progress have been obtained in identifying epitopes, reaching a high level of sensitivity and a simple analytical procedure [26,27]. However, improvements in cultivation techniques and in the construction of specific monoclonal epitopes represent important goals to be achieved.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, new promising methodologies for highthroughput generation of monoclonal antibodies mapped with epitopes against AGE have been applied and validated. For example, recent studies have allowed the generation of new monoclonal antibodies destined for carboxymethyllysine [26,27]. Monoclonal antibodies have the potential to detect and quantify single glycated epitopes, but the effective and specific ones currently available are limited.…”

mentioning

confidence: 99%

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Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

Perrone

Giovino

Benny

et al. 2020

Oxidative Medicine and Cellular Longevity

252

219

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The advanced glycation end products (AGEs) are organic molecules formed in any living organisms with a great variety of structural and functional properties. They are considered organic markers of the glycation process. Due to their great heterogeneity, there is no specific test for their operational measurement. In this review, we have updated the most common chromatographic, colorimetric, spectroscopic, mass spectrometric, and serological methods, typically used for the determination of AGEs in biological samples. We have described their signaling and signal transduction mechanisms and cell epigenetic effects. Although mass spectrometric analysis is not widespread in the detection of AGEs at the clinical level, this technique is highly promising for the early diagnosis and therapeutics of diseases caused by AGEs. Protocols are available for high-resolution mass spectrometry of glycated proteins although they are characterized by complex machine management. Simpler procedures are available although much less precise than mass spectrometry. Among them, immunochemical tests are very common since they are able to detect AGEs in a simple and immediate way. In these years, new methodologies have been developed using an in vivo novel and noninvasive spectroscopic methods. These methods are based on the measurement of autofluorescence of AGEs. Another method consists of detecting AGEs in the human skin to detect chronic exposure, without the inconvenience of invasive methods. The aim of this review is to compare the different approaches of measuring AGEs at a clinical perspective due to their strict association with oxidative stress and inflammation.

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“…Several anti-AGE antibodies have been produced by immunization of animals with AGEs generated either from total synthesis or through in vitro glycation methods. Such methods involve the incubation of an immunogenic carrier protein, such as BSA, with glucose or other reactive sugar metabolites. − Reaction conditions that generate glucosepane are known also to generate a range of AGE byproducts, including carboxymethyllysine. , …”

Section: Introductionmentioning

confidence: 99%

Generation and Characterization of Anti-Glucosepane Antibodies Enabling Direct Detection of Glucosepane in Retinal Tissue

et al. 2020

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Although there is ample evidence that the advanced glycation end-product (AGE) glucosepane contributes to age-related morbidities and diabetic complications, the impact of glucosepane modifications on proteins has not been extensively explored due to the lack of sufficient analytical tools. Here, we report the development of the first polyclonal anti-glucosepane antibodies using a synthetic immunogen that contains the core bicyclic ring structure of glucosepane. We investigate the recognition properties of these antibodies through ELISAs involving an array of synthetic AGE derivatives and determine them to be both high-affinity and selective in binding glucosepane. We then employ these antibodies to image glucosepane in aging mouse retinae via immunohistochemistry. Our studies demonstrate for the first time accumulation of glucosepane within the retinal pigment epithelium, Bruch’s membrane, and choroid: all regions of the eye impacted by age-related macular degeneration. Co-localization studies further suggest that glucosepane colocalizes with lipofuscin, which has previously been associated with lysosomal dysfunction and has been implicated in the development of age-related macular degeneration, among other diseases. We believe that the anti-glucosepane antibodies described in this study will prove highly useful for examining the role of glycation in human health and disease.

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Generation and characterization of monoclonal antibody against Advanced Glycation End Products in chronic kidney disease

Cited by 6 publications

References 29 publications

How do Uremic Toxins Affect the Endothelium?

How do Uremic Toxins Affect the Endothelium?

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

Generation and Characterization of Anti-Glucosepane Antibodies Enabling Direct Detection of Glucosepane in Retinal Tissue

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