How healthy are the various cooking methods? The answer depends on what you cook and how you cook it. If your idea of a healthy main course is blackened fish, crispy fried chicken, or caramelized ribs, youve probably never heard of advanced Glycated End Products (also known as advanced glycated end products).. Advanced glycated end products, which were discovered by Louis Maillard in 1912, are a class of chemical byproducts that result from the combination of protein and sugar (usually glucose) when food is cooked by excessive heat.1. Advanced glycated end products can also be formed by the body when too much refined sugar is eaten and elevated blood sugar levels are maintained for too long a time. And food manufacturers intentionally increase the number of advanced glycated end products in food, either by adding sugar or by browning food elements.. Advanced glycated end products arent to be confused with glycoproteins, even though they share the same building blocks. A glycoprotein forms when ...
Advanced Glycosylation End Products: Products derived from the nonenzymatic reaction of glucose and proteins in vivo that exhibit a yellow-brown pigmentation and an ability to participate in protein-protein cross-linking. These substances are involved in biological processes relating to protein turnover and it is believed that their excessive accumulation contributes to the chronic complications of diabetes mellitus.
This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III β-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 μg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA
Compare Advanced Glycosylation End Product-specific Receptor ELISA Kits from Rockland Immunochemicals, Inc. from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more.
糖腎病是一種常見的慢性糖尿病併發症,也是造成末期腎臟衰竭的原因之一,伴隨的尿毒症狀更是讓洗腎人口數向上攀升。約有20-30%的糖尿病患者會發展成糖腎病,其中第一型糖尿病在10-15年內會演變成糖腎病,並具有50%的機會進展到末期腎病變;而第二型糖尿病則有20%-40%的糖腎病進程,然而20年後僅有20%的機率形成末期腎病變。根據美國腎臟資料系統的末期腎臟病年報中顯示,台灣糖腎病患者的盛行率位居世界第二,發生率則居全球之冠,在國人十大死因裡更是排名第五,為此研發出延緩或改善糖尿病腎病變的治療方法是極其迫切的議題。 糖尿病患者體內的高血糖環境會促進最終糖化蛋白的合成 (Advanced Glycosylation End Products, AGEs) ,進而引發體內細胞產生有害的活性氧物 (Reactive oxygen species, ROS) 以及釋放促發炎因子,造成內皮細胞受損並吸引巨噬細胞前來浸潤
TY - JOUR. T1 - Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts. AU - Spadaccio, Cristiano. AU - De Marco, Federico. AU - Di Domenico, Fabio. AU - Coccia, Raffaella. AU - Lusini, Mario. AU - Barbato, Raffaele. AU - Covino, Elvio. AU - Chello, Massimo. PY - 2014/3. Y1 - 2014/3. N2 - Background Advanced glycation endproducts (AGEs) and its receptors (RAGEs) are heterogeneous signaling proteins associated to diabetes and responsible of endothelial alterations leading to atherosclerosis progression and graft failure. The aim of this study was to investigate the role of statin in reducing AGEs related endothelial damage. Methods Endothelial cell(EC) obtained from leftovers of saphenous vein grafts of non-diabetic patients were incubated with AGEs (2 and 20 μM) and subsequently treated with Simvastatin. Neutrophils (PNM) adherence, ROS production and RAGE and peroxisome proliferator-activated receptors-gamma (PPAR-γ) ...
This is the second in a series of articles designed to provide important information about key metabolic processes that are really important to understand for optimizing our quality of life - and yet almost no one in the general public has any awareness of them at all.. The first article addressed methylation: an important biochemical process in our bodies that is important for many health issues. Here is a link to the article.. This article addresses another very important metabolic process:. Advanced Glycation End Products (AGEs).. What exactly are Advanced Glycation End Products (AGEs)? Here is a great description of what AGEs are:. Advanced Glycation End Products (AGEs) are basically the nasty by-products of glucose metabolism. The typical Western Diet, coupled with a sedentary lifestyle, too much fat, and insulin resistance, leaves our bodies churning out excess glucose and unable to burn it. It stays in our blood stream too long and there it does incredible damage.. One of the most ...
PURPOSE: Advanced glycation endproduct (AGE) formation on the basement membrane of retinal capillaries has been previously described but the impact of these adducts on capillary endothelial cell function vascular repair remains uncertain. This invest
Advanced glycation endproducts (AGEs) are primarily known as a complication in diabetic patients through their mediation of the inflammatory response. However, a variety of studies have demonstrated enhanced formation of AGEs in cardiovascular disorders. Despite the large number of AGEs produced during the Maillard reaction, recent focus is on the major non-crosslinking AGE Nε-carboxymethyllysine. Kneyber and colleagues focused on sepsis-induced cardiac dysfunction and investigated whether myocardial inflammation is associated with enhanced cardiac AGE deposition and whether this is further enhanced by mechanical ventilation. They showed that both conditions are associated with enhanced AGE deposition and myocardial inflammation. Therefore, AGEs may participate in the inflammatory response related to cardiac dysfunction in critically ill patients. Moreover, life-saving ventilation stimulates AGE formation in these patients. This interesting study raises the question of whether AGEs in critically ill
TY - JOUR. T1 - Integral role of receptor for advanced glycation end products (RAGE) in nondiabetic atherosclerosis. AU - Uekita, Hironori. AU - Ishibashi, Toshiyuki. AU - Shiomi, Masashi. AU - Koyama, Hidenori. AU - Ohtsuka, Shukuko. AU - Yamamoto, Hiroshi. AU - Yamagishi, Shoichi. AU - Inoue, Hiroyoshi. AU - Itabe, Hiroyuki. AU - Sugimoto, Koichi. AU - Kamioka, Masashi. AU - Ohkawara, Hiroshi. AU - Wada, Ikuo. AU - Yasuchika, Takeishi. PY - 2019/1/1. Y1 - 2019/1/1. N2 - An advanced glycation end products (AGE)/a receptor for AGE (RAGE) axis plays a central role in the pathogenesis of diabetic vascular remodeling. This study was conducted to clarify the role of RAGE in nondiabetic atherosclerosis. We used the aortic and coronary atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits prone to myocardial infarction (WHHLMI) at 1 to 14 months. Immunohistochemistry demonstrated the significant expression of RAGE as early as at 1 month with the stronger expression at 3 and 7 ...
Clearance of apoptotic cells by macrophages and other phagocytic cells, called efferocytosis, is a central process in the resolution of inflammation. Although the receptor for advanced glycation end products (RAGE) has been shown to participate in a variety of acute and chronic inflammatory processes in the lungs and other organs, a role for RAGE in efferocytosis has not been reported. In the present studies, we examined the potential involvement of RAGE in efferocytosis. Macrophages from transgenic RAGE-/- mice showed a decreased ability to engulf apoptotic neutrophils and thymocytes. Pretreatment of RAGE+/+ macrophages with advanced glycation end products, which competitively bind to RAGE, or Abs against RAGE diminished phagocytosis of apoptotic cells. Overexpression of RAGE in human embryonic kidney 293 cells resulted in an increased ability to engulf apoptotic cells. Furthermore, we found that incubation with soluble RAGE enhances phagocytosis of apoptotic cells by both RAGE+/+ and RAGE-/- ...
Determine if an acute glucose load (50g) is associated with an in-vivo and in-vitro increase in the concentration of Advanced Glycation End Products (AGEPs) that, in turn, can impact vascular endothelial reactivity and induce an acute increase in blood pressure. Previous studies generated in the investigators laboratory showed that circulating soluble Receptor for Advanced Glycation End Products (sRAGE) and Tumor Necrosis Factor (TNF)-a (mediator of acute inflammation) are considered markers of the extent of maternal RAGE activation and/or systemic inflammation, respectively ...
Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the
3. Ma, H., Li, S., Xu, P., Babcock, S.A., Dolence, E.K., Brownlee, M., Li, J., and Ren, J., Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) upregulation contribute to the onset of diabetic cardiomyopathy. Journal of Cellular and Molecular Medicine (2009), 13(8b), 1751-64. ...
TY - JOUR. T1 - Anti-receptor for advanced glycation end products therapies as novel treatment for abdominal aortic aneurysm. AU - Zhang, Fan. AU - Kent, K. Craig. AU - Yamanouchi, Dai. AU - Zhang, Yan. AU - Kato, Kaori. AU - Tsai, Shirling. AU - Nowygrod, Roman. AU - Schmidt, Ann Marie. AU - Liu, Bo. PY - 2009/9/1. Y1 - 2009/9/1. N2 - OBJECTIVE:: Rupture of abdominal aortic aneurysms (AAA) is a devastating event potentially preventable by therapies that inhibit growth of small aneurysms. Receptor of advanced glycation end products (RAGE) has been implicated in age related diseases including atherosclerosis and Alzheimer. Consequently, we explored whether RAGE may also contribute to the formation of AAAs. RESULTS:: Implicating a role for RAGE in AAA, we found the expression of RAGE and its ligand AGE were highly elevated in human aneurysm specimens as compared with normal aortic tissue. In a mouse model of AAA, RAGE gene deletion (knockout) dramatically reduced the incidence of AAA to 1/3 of ...
Protein glycation, induced by hyperglycemia, is implicated in the appearance of diabetic complications and the aging process. Glycation involves the non-enzymatic reaction between sugars and protein amino groups that lead to formation of advanced glycation end products (AGEs). When aminoguanidine, a proven AGE inhibitor, was tested as an anti-diabetic drug in clinical trials showed critical side effects, which suggested a need for improved AGE inhibitors. A protein glycation model included histone H1 and glyoxal or methylglyoxal since it allowed to distinguish AGE inhibitors from antioxidants. This book describes the findings of Dr Cervantes and graduate student, Srinath Pashikanti, of novel natural product AGE inhibitors and the in vivo modification of nuclear proteins, histone H1, with AGE adducts. Rutin metabolic derivatives were tested as AGEs inhibitors since rutin, a flavonoid consumed in fruits and vegetables, is metabolized in the gut. These results suggest effective ...
Advanced glycation end products (AGEs) are critically involved in atherogenesis in diabetes by binding to receptors for AGE (RAGEs) in vascular cells, thus inducing the expression of proinflammatory mediators. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development. Therefore, limiting RAGE expression might be an intriguing concept to modulate vascular disease in diabetic patients. The present study investigated whether thiazolidinediones (TZDs), antidiabetic agents clinically used to treat patients with type 2 diabetes, might modulate endothelial RAGE expression. Stimulation of human endothelial cells with rosiglitazone or pioglitazone decreased basal as well as tumor necrosis factor-α-induced RAGE cell surface and total protein expression. In addition, TZDs reduced RAGE mRNA expression in endothelial cells. These effects on RAGE expression were caused by an inhibition of nuclear factor-κB (NF-κB) activation at the proximal NF-κB site of the ...
In patients with type 2 diabetes mellitus (T2DM), atherosclerosis continues to pose a challenge due to its high prevalence, but also because it is particularly reluctant to revascularization therapies (1,2). Moreover, while the detrimental effect of hyperglycemia in developing coronary disease has been firmly established (3,4), the preventive effects of glucose-lowering therapies have been disappointing (5).. There is an important debate, still open, concerning the mechanisms linking hyperglycemia and vascular damage, particularly those related to mitochondrial activity (6). Increasing evidence supports the notion that elevated glucose metabolism adds to inflammation synergistically rather than acting per se (7). Nevertheless, it is very well known that high glucose can also induce nonenzymatic protein glycation (8) that may prevail after normalization of glycemia. Either intermediate Amadori adducts and advanced glycosylation end products (AGEs) have been reported to produce vascular damage, ...
Advanced glycosylation endproducts (AGEs), the glucose-derived adducts that form nonenzymatically and accumulate on tissue proteins, are implicated in many chronic complications associated with diabetes and aging. We have previously described a monocyte/macrophage surface receptor system thought to coordinate AGE protein removal and tissue remodeling, and purified a corresponding 90-kD AGE-binding protein from the murine RAW 264.7 cell line. To identify AGE-binding proteins in normal animals, the tissue distribution of 125I-AGE rat serum albumin taken up from the blood was determined in rats in vivo. These uptake studies demonstrated that the liver was a major site of AGE protein sequestration. Using a solid-phase assay system involving the immobilization of solubilized membrane proteins onto nitrocellulose to monitor binding activity, and several purification steps including affinity chromatography over an AGE bovine serum albumin matrix, two rat liver membrane proteins were isolated that ...
Certain Advanced Glycation End products (AGEs) Increase the risk of Complications in Diabetes: New study at the Joslin Diabetes Center has revealed that patients of Type 1 diabetes with higher levels of carboxyethyl-lysine and pentosidine AGEs are 7.2-fold more likely to have any complication. Earlier studies had revealed that these AGEs are linked more to fructose. [Sun JK et al. Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration: The Joslin 50-Year Medalist Study. Diabetes Care 29 March, 2011;34(4):968-974. doi: 10.2337/dc10-1675 Full Text , Mikulíková K, Eckhardt A, Kunes J, Zicha J, Miksík I. Advanced glycation end-product pentosidine accumulates in various tissues of rats with high fructose intake. Physiol Res. 2008;57(1):89-94. Epub 2007 Feb 8. Full text , Krajčovičova-Kudlačkova M, Šebekova K, Schinzel R, Klvanova J. Advanced Glycation End Products and Nutrition. Physiol. Res. 2002;51:313-316. Full text ...
FUNCTION: Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF- alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular ...
FUNCTION: Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF- alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular ...
From BioPortfolio: The accumulation of advanced glycation endproducts in articular cartilage has been suggested as an etiologic factor in the development and progression of knee o...
Advanced glycation end products (AGEs) have been introduced to be involved in the pathogenesis of osteoarthritis (OA). The influence of AGEs on osteoarthritic fibroblast-like synovial cells (FLS) has been incompletely understood as yet. The present study investigates a potential influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth, and on the expression of proinflammatory and osteoclastogenic markers in cultured FLS. FLS were established from OA joints and stimulated with AGE-BSA. The mRNA expression of p27Kip1, RAGE (receptor for AGEs), nuclear factor kappa B subunit p65 (NFκB p65), tumor necrosis factor alpha (TNF-α, interleukin-6 (IL-6), receptor activator of NFκB ligand (RANKL) and osteoprotegerin was measured by real-time PCR. The respective protein expression was evaluated by western blot analysis or ELISA. NFκB activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and
Glucose can react non-enzymatically with amino groups of, for example, proteins, to yield derivatives termed advanced glycation end products (AGE), which contribute to many chronic progressive diseases associated with microvascular complications. The study aimed to determine the effect of AGE-modified albumin on THP-1 cells and human monocyte-derived macrophages. Bovine serum albumin (BSA) or human serum albumin (HSA), modified by glucose-derived AGE, was prepared by incubation with glucose for differing periods of time. Alternatively, BSA was incubated with sodium cyanoborohydride and glyoxylic acid to produce N(epsilon)-(carboxymethyl)lysine-modified BSA (CML-BSA). Stimulation for 24h of THP-1 cells with BSA, incubated for 6-8 weeks with glucose, induced significant VEGF release. Human monocyte-derived macrophages stimulated with extensively glycated HSA also showed significant VEGF release, as well as upregulation of IL-8 production, incubation for 6h with extensively glycated HSA increased release
Diabetes is the leading cause of ESRD because diabetic nephropathy develops in 30 to 40% of patients. Diabetic nephropathy does not develop in the absence of hyperglycemia, even in the presence of a genetic predisposition. Multigenetic predisposition contributes in the development of diabetic nephropathy, thus supporting that many factors are involved in the pathogenesis of the disease. Hyperglycemia induces renal damage directly or through hemodynamic modifications. It induces activation of protein kinase C, increased production of advanced glycosylation end products, and diacylglycerol synthesis. In addition, it is responsible for hemodynamic alterations such as glomerular hyperfiltration, shear stress, and microalbuminuria. These alterations contribute to an abnormal stimulation of resident renal cells that produce more TGF-1. This growth factor upregulates GLUT-1, which induces an increased intracellular glucose transport and D-glucose uptake. TGF-1 causes augmented extracellular matrix ...
The receptor for advanced glycosylation end products (RAGE) is a multiligand receptor involved in diverse cell signaling pathways. Previous studies show that this gene expresses several splice variants in human, mouse, and dog. Alternative splicing (AS) plays an important role in expanding transcriptomic and proteomic diversity, and it has been related to disease. AS is also one of the main evolutionary mechanisms in mammalian genomes. However, limited information is available regarding the AS of RAGE in a wide context of mammalian tissues. In this study, we examined in detail the different RAGE mRNAs generated by AS from six mammals, including two primates (human and monkey), two artiodactyla (cow and pig), and two rodentia (mouse and rat) in 6-18 different tissues including fetal, adult, and tumor. By nested reverse transcription-polymerase chain reaction (RT-PCR) we identified a high number of splice variants including noncoding transcripts and predicted coding ones with different potential ...
BACKGROUND/AIMS:Our previous report showed that IgG levels are strongly correlated with the indocyanine green (ICG) retention rate in patients with liver cirrhosis (LC). This correlation suggests that hyperglobulinemia in LC could be explained by impairment of hepatic removal function. To estimate IgG turnover in LC, in the present paper was determined the advanced glycation end-products (AGE) on IgG as a marker of half-life.METHODOLOGY:Serum samples were obtained from patients with LC, rheumatoid arthritis (RA), and Sjögren syndrome (SjS), and from age-matched control patients. IgG was purified from serum by the protein G-based affinity method, concentrated by filtration, and used for assay of Nepsilon-(carboxymethyl) lysine (CML), a predominant AGE, by ELISA.RESULTS:CML on IgG was significantly lower in patients with LC than in control patients, whereas there was no significant difference in total serum CML levels among patients with LC, RA, and SjS, and control patients. CML levels on IgG ...
The present invention relates to compositions and methods for inhibiting protein aging. Accordingly, a composition is disclosed which comprises an agent or compound capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. Suitable agents may contain an active nitrogen-containing group, such as a hydrazine group. Particular agents comprise aminoguanidine, α-hydrazinohistidine and mixtures thereof. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
Cooking meat at high temperatures, such as when grilling, creates "advanced glycosylation end products," or AGEs, which crank up inflammation. According to research conducted at Mount Sinai School of Medicine in New York City, inflammation rose 35 percent in diabetics who ate large quantities of AGEs, but it fell 20 percent in those who ate low levels of AGEs (Proceedings of the National Academy of Sciences, 2002, vol. 99, no. 24). High levels of AGEs are also found in some cheeses, soy sauces, pretzels, and diet sodas.. 4. Saturated fats ...
For your diabetes, we will use the iummunotherapy to treat you. The long time diabetes, there are some toxin and the advanced glycosylation end products and some immuno complex have been accumulated in your whole body especially your kidneys and blood. These things can cause inflammation reaction in kidneys and cause the kdiney damaged. Therefore,…
Sugar-damaged proteins turn yellowish-brown and are called advanced glycosylation end products (A.G.E.). The process is similar the browning a chicken where the skin gets crispy. We are all undergoing this browning process as we age. Research shows the main culprit in AGE is high glucose levels in the blood. Simple sugars appear to be the most damaging. A diet consistently high in simple sugars shortens lifespan and increases all the negative outcomes of brain aging ...
Inhibition of advanced glycation end-product formation on eye lens protein by rutin - Br J Nutr. 2011 Aug 25:1-9 - Formation of advanced glycation end products (AGE) plays a key role in the several pathophysiologies associated with ageing and diabetes, such as arthritis, atherosclerosis, chronic renal insufficiency, Alzheimers disease, nephropathy, neuropathy and cataract. This raises the possibility of inhibition of AGE formation as one of the approaches to prevent or arrest the progression of diabetic complications. Previously, we have reported that some common dietary sources such as fruits, vegetables, herbs and spices have the potential to inhibit AGE formation. Flavonoids are abundantly found in fruits, vegetables, herbs and spices, and rutin is one of the commonly found dietary flavonols. In the present study, we have demonstrated the antiglycating potential and mechanism of action of rutin using goat eye lens proteins as model proteins. Under in vitro conditions, rutin inhibited ...
Sustained hyperglycemia is closely associated with increased risk to develop nephropathy. We have previously reported alterations in the intrarenal oxygen metabolism already after the early onset of diabetes. Furthermore, formation of advanced glycation end-products (AGE) is postulated as a major contributor to diabetic nephropathy. We therefore investigated the possible relationship between altered oxygen metabolism and AGE in diabetic kidneys.Normoglycemic and streptozotocin-diabetic rats with and without chronic treatment with aminoguanidine (AGE inhibitor; 600 mg/kg bw/24 h in drinking water) or L-N6-(1-Iminoethyl)lysine (L-NIL, iNOS inhibitor, 1 mg/kg bw/24 h in drinking water) were studied 2 weeks after induction of diabetes. Glomerular filtration rate (GFR) was estimated by inulin clearance, oxygen tension (pO2) and interstitial pH by microelectrodes and regional renal blood flow (RBF) by laser-Doppler. Histological changes were evaluated on fixed tissue.Glomerular hyperfiltration was ...
Due to their lower production cost compared with monoclonal antibodies, single-chain variable fragments (scFvs) have potential for use in several applications, such as for diagnosis and treatment of a range of diseases, and as sensor elements. However, the usefulness of scFvs is limited by inhomogeneity through the formation of dimers, trimers, and larger oligomers. The scFv protein is assumed to be in equilibrium between the closed and open states formed by assembly or disassembly of VH and VL domains. Therefore, the production of an scFv with equilibrium biased to the closed state would be critical to overcome the problem in inhomogeneity of scFv for industrial or therapeutic applications. In this study, we obtained scFv clones stable against GA-pyridine, an advanced glycation end-product (AGE), by using a combination of a phage display system and random mutagenesis. Executing the bio-panning at 37 °C markedly improved the stability of scFvs. We further evaluated the radius of gyration by small-angle
The non-enzymatic reaction of reducing carbohydrates with lysine side chains and N-terminal amino groups of macromolecules (proteins, phospholipids and nucleic acids) is called the Maillard reaction or glycation. The products of this process, termed advanced glycation end products (AGE), adversely affect the functional properties of proteins, lipids and DNA. We offer a variety of antibodies and assays to study universal AGE formation (e.g. our AGE ELISA Kits) as well as specific AGE species such as CML, CEL and MG.
Anti-Age Day Cream Anti-Age A smooth finishing cream to deliver a well hydrated and plump finish to the skin after treatment and for daily use.
Receptor for advanced glycation products (RAGE) is a multiligand receptor on vascular cells and plays an important role in the progression of diabetic complications. To define if RAGE modulates atherosclerosis under non-diabetic conditions, we examined the effect of RAGE deficiency in non-diabetic mice with hyperlipidemia. RAGE knockout mice (RAGE−/−) were bred with low-density lipoprotein receptor knockout (LDLr−/−) mice to generate the double knockout (DKO) mice. The mice were fed with western diet for 12 weeks, and aortic atherosclerotic lesions were analyzed histologically. Although there was no difference in body weight, fasting blood glucose and serum AGE levels between DKO and LDLr−/− mice, DKO mice exhibited a significant decrease in the size and macrophage content in atherosclerosis lesions compared with LDLr−/− mice. Expressions of endothelial adhesion molecules such as VCAM-1 and ICAM-1 in the aorta were lower in DKO mice than those in LDLr−/− mice. ...
Idiopathic pulmonary fibrosis (IPF) is a debilitating disease that involves a severe reduction in respiratory function, essentially culminating in the loss of the ability to sufficiently breathe. Current therapies are largely ineffective, and many of the molecular details of the pathogenesis of IPF remain unknown. Thus, new therapeutic targets need to be identified.We investigated a possible role for the receptor for advanced glycation end products (RAGE) in the pathogenesis of IPF. RAGE is a multiligand member of the immunoglobulin superfamily of cell surface receptors. It is generally associated with cellular perturbation in that RAGE-ligand interactions initiate a signaling cascade that ends with the activation of the pro-inflammatory transcription factor NF-kappaB. In most adult healthy tissues RAGE is expressed at low levels, but it is highly upregulated at sites of various pathologies, where it is thought to act as a propagation factor for disease. Notably, the exception to low RAGE ...
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.
The metabolic syndrome (MetSyn), a well-defined cluster of pathogenic conditions, includes glucose intolerance, insulin resistance (pre-diabetes), hypertension, abdominal obesity, and dyslipidemia. The MetSyn has a strong inflammatory component and raises the risk for cardiovascular disease (CVD) by five-fold and of diabetes by two fold in aging. Although, excessive caloric intake, i.e. over nutrition is known to be involved in developing the MetSyn, the actual causative agents of MetSyn in human nutrition have not been determined.. The investigators have previously shown that Advanced Glycation End products (AGEs) can induce oxidant stress and inflammatory responses and modulate insulin signaling in animal models and more recently in humans. These studies separated the effects of over-nutrition from the pro-inflammatory effects of AGEs, a factor not previously considered. These data support our hypothesis that AGE-restriction could be an important intervention in the MetSyn in aging.. The ...
Both advanced glycation end products and vascular endothelial growth factor are believed to play a role in the pathogenesis of diabetic retino pathy. It is known that vascular endothelial growth facto
Advanced glycation end products naturally form in our bodies from the chemical reaction of sugars with proteins. How can you limit your AGE intake?
Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization.Methods: Male Wistar rats were intraperitoneally injected with control (C) or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass spectrometry and ELISA
The pathological role of advanced glycation end products (AGEs) and of oxidative-carbonylic stress is well known in the context of diabetes. Moreover, there is also strong evidence that they play a ...
The reaction between reducing sugars and protein free amines, known as the Maillar reaction results in the formation of advanced glycation endproducts (AGEs). AGE modification changes the structure of proteins to amyloid cross-beta structure. These protein structures can activate receptors known as RAGE on glial cells (microglia and astrocytes), and induce the expression of inducible nitric oxide synthase (iNOS). Activation of inducible nitric oxide synthase in glial cells is assumed to contribute to oligodendrocyte degeneration in demyelinating diseases (e.g. multiple sclerosis) and neuronal death during Alzheimers Disease (AD). Our goal was to study AGE-activated signal transduction pathways involved in the induction of iNOS in the rat microglial cells. In vitro prepared AGE-BSA used as model AGE, induces nitric oxide (NO). We treated the Cultured Microglial cell with different range of glycated BSA (low-glycated-BSA to Advanced Glycated End-BSA) and BSA which conserved against glycation in the
The present invention is directed to compositions and devices based upon the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions and devices having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.
To assess regulation of cell surface expression of ICAM-1 by the interaction of AGEs with RAGE, HSVEC were incubated with AGE albumin. A dose-dependent increase in cell surface expression of ICAM-1 was noted compared with native albumin (Figure 4b, lanes 2, 3, 4, and 1, respectively). This effect was mediated at least in part by RAGE, as demonstrated by decreased AGE-mediated expression of ICAM-1 in the presence of anti-RAGE IgG but not by nonimmune IgG (Figure 4b, lanes 7 and 8, respectively). In vivo-derived uremic AGEs had similar effects; compared with native albumin, incubation of HSVECs with uremic AGEs resulted in an ≈1.7-fold increase in cell surface expression of ICAM-1 (Figure 4b, lanes 9 and 10, respectively). These effects were mediated in part by RAGE, as demonstrated by reduced expression of ICAM-1 in the presence of anti-RAGE IgG but not by nonimmune IgG (Figure 4b, lanes 11 and 12, respectively).. Because E-selectin mediates targeting of inflammatory cells, particularly ...
Glycation of proteins leads to the formation of advanced glycation endproducts (AGEs) of diverse molecular structure and biological function. Serum albumin derivatives modified to minimal and high extents by methylglyoxal and glucose in vitro have been used in many studies as model AGE proteins. The early and advanced glycation adduct contents of these proteins were investigated using the 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of enzymic hydrolysates. AGEs derived from methylglyoxal, glyoxal and 3-deoxyglucosone, the hydroimidazolones Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), Nδ-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) and Nδ-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine (3DG-H1), bis(lysyl)imidazolium cross-links methylglyoxal-derived lysine dimer (MOLD), glyoxal-derived lysine dimer (GOLD), 3-deoxyglucosone-derived lysine dimer (DOLD), monolysyl adducts N∊-(1-carboxyethyl)lysine (CEL), N∊-carboxymethyl-lysine ...
Skin autofluorescence (AF) for the non-invasive assessment of the amount of accumulated tissue Advanced Glycation Endproducts (AGEs) increases with aging. In subjects with darker skin colors, measurements typically result in lower AF values than in subjects with fair skin colors, e.g. due to selective absorption by skin compounds. Our aim was to provide a new method for calculating skin AF, yielding values that are independent of skin color. The deviation of skin AF of healthy subjects with various darker skin types (N = 99) compared to reference values from Caucasians showed to be a function of various parameters that were derived from reflectance and emission spectra in the UV and visible range (adjusted R2 = 80%). Validation of the new algorithm, based on these findings, in a separate dataset (N = 141) showed that results of skin AF can now be obtained to assess skin AGEs independently of skin color.. ©2010 Optical Society of America. Full Article , PDF Article ...