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Standard curves of type I, III, IV collagen and elastin subjected and not subjected to glycation in the ELISA assay
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The most abundant proteins in the arteries are those of extracellular matrix, ie. collagen and elastin. Due to their long half-lifes these proteins have an increased chance to undergo glycation. The aim of this study was to determine relationship between the content of the main extracellular matrix proteins and the advanced glycation end products (...
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Citations
... AGEs accumulation can take place both intracellularly, where these compounds occur in the form of dicarbonyl precursors of glucose derivatives, and in extracellular structures, e.g. in the skin, nervous tissue, blood vessels, kidneys, heart [45,[73][74][75]. The accumulation of AGEs in cells may lead to the activation of intracellular signaling pathways, to modification of proteins, and thus often their complete inactivation [76,77]. ...
... In COVID-19, glycation would affect the ACE2 receptor [173]. In addition, glycation may prevent the modified antigens from interacting with the antibodies, or the glycated antibodies may not be able to react with the antigens which impairs the serological immune response [77,173]. AGEs are known to stimulate the classical complement pathway, thereby enhancing the formation of membrane attack complexes and the overall destruction of lung parenchyma as a result of COVID-19 infection [174]. ...
... Note intact multisynaptic bouton in perivascular region immediately adjacent to a blast damaged vessel. Scale, 2 µm in a, b, bonds [86], but additional protein cross-linking takes place over time by advanced glycation end-products [7,61,84], which interferes with immunodetection [48]. It is well established that immunological detection of collagen type IV in normal adult rodents (but not in embryos and young animals) requires pretreatment with a protease (i.e., pepsin) to expose the antibody-recognized epitopes [26]. ...
In the course of military operations in modern war theaters, blast exposures are associated with the development of a variety of mental health disorders associated with a post-traumatic stress disorder-related features, including anxiety, impulsivity, insomnia, suicidality, depression, and cognitive decline. Several lines of evidence indicate that acute and chronic cerebral vascular alterations are involved in the development of these blast-induced neuropsychiatric changes. In the present study, we investigated late occurring neuropathological events associated with cerebrovascular alterations in a rat model of repetitive low-level blast-exposures (3 × 74.5 kPa). The observed events included hippocampal hypoperfusion associated with late-onset inflammation, vascular extracellular matrix degeneration, synaptic structural changes and neuronal loss. We also demonstrate that arteriovenous malformations in exposed animals are a direct consequence of blast-induced tissue tears. Overall, our results further identify the cerebral vasculature as a main target for blast-induced damage and support the urgent need to develop early therapeutic approaches for the prevention of blast-induced late-onset neurovascular degenerative processes.
... Elastin is highly elastic and is found in connective tissues, allowing many tissues in the body to regain their original shape after stretching or contracting. It is particularly abundant in large elastic vessels such as the aorta (Kuzan et al., 2018). Hyaluronic acid is a glycosaminoglycan composed of the basic structure of disaccharides (D-glucuronic acid and N-acetylglucosamine). ...
Bio-glues are gaining ground in medical research to close wounds and fight infections. Among them, the most promising bio-glue is the one prepared from natural materials (fibrin, gelatin, polysaccharides, etc.). Most of these materials are components of the extracellular matrix (ECM) and possess excellent biocompatibility, biodegradability and mechanical strength, which facilitate wound repair. However, there are no studies that utilize the decellularized materials to prepare bio-glues. Outside the wound sealants, approaches that utilize the ECM scaffold to promote tissue repair show tremendous potential. Experimentally, it is unknown if ECM can be successfully transformed to the bio-glue, either alone or in combination with nature biomaterials. In this review, we outline the first attempts at the potential of using ECM to prepare bio-glue for wound repair during the surgery.
... Glycation is a non-enzymatic process involving reducing sugar and amino groups of proteins, which contributes to the formation of advanced glycation end products (AGEs). These products have significantly altered biochemical properties relative to the substrates, including proteins that have altered conformation, increased rigidity, resistance to proteolysis, etc. [106,107]. ...
Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children.
... The reason for this result is most likely the disclosure with an enzyme of epitopes, inaccessible to antibodies inside the molecule. However, it is worth adding that the cross-links characteristic of glycation are not fully susceptible to enzymatic activity 24 . In addition, the results of both analyzes correlate quite closely with each other (r= 0.7517, p<0.0001), it means that it is possible to simplify test in order to obtain reliable results without proteinase K. ...
Glycation is a non-enzymatic process involving the reaction of reducing sugars or reactive oxoaldehyde with proteins, lipids or nucleic acids, which results in the formation of advanced glycation end products (AGEs). The presented work discusses the glycation process in people with advanced stage of type 1 or type 2 diabetes. The concentration of different AGEs and their receptors for 58 serum samples was determined by ELISA and by spectrofluorimetric methods. In addition to fluorescent low molecular weight and protein-bound AGEs, we have also marked a new class of AGEs: melibiose-derived glycation product (MAGE). Our attention was also focused on the two groups of AGEs receptors: scavenger receptors (SR-A and SR-B) and RAGE. The correlation between the SR-AI scavenging receptors concentration and the fluorescence of AGEs as well as diabetes biological markers: GFR, creatinine contentration and HbA1c was demonstrated. A relationship between the concentration of AGEs and their receptors was also found in serum sample of patients treated with the metformin and aspirin. Furthermore, the concentration of SR-AI scavenger and the fluorescence of total AGEs was significantly lower in treated patients than in non treated patients. AGEs have also been found to contribute to the development of cardiovascular disease, atherosclerosis and diabetic complications, what could be deduced from the correlation of AGEs level and HDL cholesterol or uric acid level. Thus, it was confirmed that AGEs are involved in the pathomechanism of diabetes and other degenerative diseases. Nowadays, it is believed that AGEs due to the long time remaining in the body may be an important diagnostic marker. Their determination may allow monitoring the progression of the disease and the effectiveness of the therapy.
... Results of quantitative analysis obtained by our study indicate that AGEs occur mainly within extracellular matrix. This is not astonishing, as extracellular matrix proteins like collagen are particularly susceptible to AGE modification because of slow turnover rates [19]. ...
... We also noticed that there is more MAGE in segments of thyroid gland with squamous cell carcinoma in comparison with papillary carcinoma, but this is not statistically verified. Further studies are being conducted in order to gain understanding of MAGE content in different human tissues in relations to disease [19,22]. ...
The patho-mechanism of changes in the thyroid gland, including carcinogenesis, is a complex process, which involves oxidative stress. The goal of our investigation was to verify the extent of stress in the thyroid gland related to glycation. The study samples were comprised of blood sera, thyroid, and adipose tissue sections probed from 37 patients diagnosed with thyroid cancers and goiter. Using immuno-enzymatic and fluorometric assays we analyzed the content of advanced glycation end-products (AGEs), pentosidine, receptors for advanced glycation end-products (RAGE), scavenger receptor class (SR)-A, SR-B, glutathione, malondialdehyde and nitric oxide synthase. In addition to classic AGEs, a recent study detected the melibiose-derived glycation (MAGE) product. We demonstrated the presence of AGEs, MAGE and their receptors of the RAGE and SR-A. In addition, in the control samples of thyroid glands SR-B groups were detected as well as of pathological groups without noticeable tendency to antigen concentration in the area of carcinogenesis. Fluorescent AGEs correlate positively with glutathione, which supports the assumption that glycation stress leads to augmentation of oxidative stress and increase of the intensity of antioxidant mechanisms.
... Additionally, a multitude of conditions that can influence the glycation of AGEs (such as pH, presence and the amount of free radicals and metal ions, amongst others), and the type and concentration of substrates need to be taken into consideration (4). Moreover, AGEs are typically present in small amounts in vivo (14,43). Their isolation from tissues can cause undesirable chemical modifications and the formation of artefacts (44). ...
... Equally popular are immunoenzymatic methods using antibodies (1,4,44,47); however, the specificity of the antibodies (11,14) or the low quantities of antigens in the sample can cause difficulties (1). The natural properties of AGEs associated with fluorescence can also be exploited in fluorometric methods (43,45,47); unfortunately, the fluorescence of other components in the sample often obfuscates the results (11). Thus, at present, there is no one specific and sensitive method to measure AGE content in samples (11). ...
Advanced glycation end-products (AGEs) are proteins or lipids glycated nonenzymatically by glucose, or other reducing sugars and their derivatives, such as glyceraldehyde, glycolaldehyde, methyloglyoxal and acetaldehyde. There are three different means of AGE formation: i) Maillard reactions, the polyol pathway and lipid peroxidation. AGEs participate in the pathological mechanisms underlying the development of several diseases, such as diabetes and its complications, retinopathy or neuropathy, neurological disorders (for example, Parkinson's disease and Alzheimer's disease), atherosclerosis, hypertension and several types of cancer. AGE levels are increased in patients with hyperglycaemia, and is likely the result of the high concentration of glycation substrates circulating in the blood. The present review summarises the formation and nomenclature of advanced glycation end-products, with an emphasis on the role of AGEs in the development of diabetes, neurological disorders, as well as in cancer and other pathologies. A particular focus is placed on the functions of toxic AGEs. Additionally, studies which have shown the cytotoxicity of glycated albumin and other AGEs are also discussed. Finally, the diagnostic relevance of AGEs as well as for targeting in therapeutic strategies are highlighted.
... It has been postulated that especially aberrations in the structure and amount of collagen types I and III can result in atherosclerosis or hypertensive heart disease [14][15][16][17] while changes within the elastin fibers may lead to supraventricular stenosis, hypertension or aneurysm [14]. Our previous study referred to the role of collagen in the arteries in the context of glycation [18] and another one shows that there is a relationship between the content of type II collagen and the degree of atherosclerosis [19]. In the present study the object of interest are other types of fibrillar collagens, i.e. type I and type III, type IV collagen and elastin. ...
Introduction:
Extracellular matrix (ECM) proteins have been associated with atherosclerotic complications, such as plaque rupture, calcification and aneurysm. It is not clear what role different types of collagen play in the pathomechanism of atherosclerosis. The aim of the study was to analyze the content of elastin and major types of collagen in the aortic wall and how they associated are with course of atherosclerosis.
Material and methods:
. In this work we present six biochemical parameters related to ECM proteins (collagen type I, III, and IV, elastin, proline and hydroxyproline) analyzed in 106 patients' aortic wall specimens characterized by different degree of atherosclerosis. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC/ESI-MS/MS), ELISA and immunohistochemical methods were used. The severity of atherosclerosis was assessed on the six-point scale of the American Heart Association, taking into account the number and location of foam cells, the presence of a fatty core, calcium deposits and other characteristic atherosclerotic features.
Results:
The results show that there is a relationship between the content of collagen-specific amino acids and development of atherosclerosis. The degree of atherosclerotic lesions was negatively correlated with the content of proline, hydroxyproline and the ratio of these two amino acids. Calcium deposits and surrounding tissue were compared and it was demonstrated that the ratio of type I collagen to type III collagen was higher in the aortic tissue than in aortic calcification areas, while the ratio of collagen type III to elastin was smaller in the artery than in the calcium deposits.
Conclusions:
We suggest that increase in collagen type III presence in the calcification matrix may stem from disorders in the structure of the type I and III collagen fibers. These anomalous fibers are likely to favor accumulation of the calcium salts, an important feature of the atheromatotic process.
... At an excitation wavelength of 365 nm, the characteristic fluorescence signal of urinary AGEs was detected at emission wavelengths of 440 nm and 490 nm, which is in agreement with the literature [4,16,17,23,24]. A higher fluorescence intensity at both 440 nm and 490 nm was observed in CKD patients in comparison with healthy subjects, which could be explained by the stimulated formation and excretion of AGEs due to oxidative stress (e.g., uremia) and activation of the renin-angiotensin system [25]. ...
Advanced glycation end products (AGEs) are a class of proteins or lipids that are non-enzymatically glycated and oxidized after contact with aldose sugars. The accumulation of AGEs results in carbonyl stress, which is characteristic for diabetes mellitus, uremia, atherosclerosis and vascular dysfunction. In recent decades, several innovative methods have been developed to measure the concentration of AGEs in blood or urine. In the present study, we evaluated the use of UV fluorescence as an alternative tool to detect urinary AGEs in four groups of well characterized chronic kidney disease (CKD) patients over a wide range of kidney insufficiency and in a group of healthy subjects. Using an excitation wavelength of 365 nm, the fluorescence spectra of urinary AGEs were recorded in the 400–620 nm emission range. When considering the emission peaks at 440 nm and 490 nm, a significantly higher AGE-specific fluorescence intensity was detected in CKD patients compared to healthy subjects (p < 0.0001 and p = 0.0001, respectively). The urinary creatinine adjusted fluorescence emission spectra in the group of CKD patients with diabetes mellitus were comparable with those of CKD patients without diabetes mellitus. Creatinine-adjusted fluorescence emission spectra were highest in CKD patients with proteinuria, moderate in CKD patients without proteinuria and lowest in healthy controls (p < 0.0001 at both emission wavelengths). In a multiple regression analysis, age, CRP and insulin treatment were predictors of fluorescence intensity at the emission wavelength of 440 nm. Age and insulin treatment were predictors at 490 nm. The presented method is a simple, cheap, alternative method to monitor the AGE-load in the CKD population.
