No abstract available.
Glycosylation End Products, Advanced

No abstract available.
Glycosylation End Products, Advanced

No abstract available.
Glycosylation End Products, Advanced* ; Lysine*

A holy grail of curing neurodegenerative diseases is to identify the main causes and mechanisms underlying neuronal death. Many studies have sought to identify these targets in a wide variety of ways, but a more important task is to identify critical molecular targets and their origins. Potential molecular targets include advanced glycation end products (AGEs) that can promote neuronal cell death, thereby contributing to neurodegenerative disorders such as Alzheimer disease or Parkinson disease. In this study, we showed that AGE-albumin (glycated albumin) is synthesized in microglial cells and secreted in the human brain. Our results provide new insight into which microglial cells can promote the receptor for AGE-mediated neuronal cell death, eventually leading to neurodegenerative diseases.
Alzheimer Disease ; Brain ; Cell Death ; Glycosylation End Products, Advanced ; Humans ; Microglia ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.
Diabetes Complications ; Diabetic Angiopathies* ; Glucose ; Glycosylation End Products, Advanced* ; Humans ; Hyperglycemia ; Risk Factors

PURPOSE: Diabetic complications are a major concern to manage progression of diabetes. Production of advanced glycation end products (AGEs) due to high blood glucose is one of the mechanisms leading to diabetic complications. Multiple pharmacologic AGE inhibitory agents are currently under development, but clinical applications are still limited due to safety issues. Thus, it is necessary to identify a safe anti-glycation agent. It is known that burdock roots have antioxidant, anti-inflammatory, and anti-cancer activities. The objective of the present study was to investigate the inhibitory role of burdock roots on the formation of high glucose-induced glycation of bovine serum albumin (BSA). METHODS: In this study, glycation of BSA by glucose, galactose, or fructose at 37℃ for 3 weeks was assessed based on levels of α-dicarbonyl compounds (early-stage glycation products), fructosamine (intermediate products of glycation), and fluorescent AGEs (late-stage glycation products). In order to compare the inhibitory actions of burdock root extract in AGE formation, aminoguanidine (AG), a pharmacological AGE inhibitor, was used as a positive control. RESULTS: BSA glycation by glucose, fructose, and galatose was dose- and time-dependently produced. Burdock root extract at a concentration of 4 mg/mL almost completely inhibited glucose-induced BSA glycation. The results demonstrate that burdock root extract inhibited AGE formation with an IC₅₀ value of 1.534 mg/mL, and inhibitory activity was found to be more effective than the standard anti-glycation agent aminoguanidine. This study identified a novel function of burdock root as a potential anti-glycation agent. CONCLUSION: Our findings suggest that burdock root could be beneficial for preventing diabetic complications.
Arctium* ; Blood Glucose ; Diabetes Complications ; Fructosamine ; Fructose ; Galactose ; Glucose ; Glycosylation End Products, Advanced ; Hyperglycemia ; Serum Albumin, Bovine

BACKGROUND AND PURPOSE: Low levels of soluble receptor for advanced glycation end products (sRAGE) are associated with three conventional vascular risk factors (3Fs: diabetes, hypertension, and hypercholesterolemia), nondiabetic coronary artery disease, and Alzheimer's disease. However, the association between sRAGE and acute ischemic stroke (AS), especially AS without a source of cardioembolism, has not yet been established. Methods: Patients with AS without a source of cardioembolism (n=259) and age-matched controls (n=300) were grouped according to the presence of 3Fs: AS patients with and without 3Fs (3Fs+ AS and 3Fs- AS, respectively) and controls with and without 3Fs (3Fs+ control and 3Fs- control, respectively). Levels of sRAGE were analyzed among the four groups. RESULTS: sRAGE was significantly higher in the controls than in the AS patients (855 pg/mL vs. 690 pg/mL, p<0.01). sRAGE was significantly higher in 3Fs- controls (996 pg/mL, p<0.05) than in 3Fs+ controls (721 pg/mL), and in AS group regardless of the 3Fs (629 pg/mL in 3Fs- and 705 pg/mL in 3Fs+). The lowest tertile of sRAGE was associated with an increased risk of AS in the 3Fs- group [adjusted odds ratio (OR) 4.0, 95% confidence interval (CI) 1.6-10.3, p<0.01] but not in the 3Fs+ group. The level of sRAGE was also correlated with neurological severity in the 3Fs- AS group (r=-0.32, p<0.05) but not in the 3Fs+ AS group. CONCLUSIONS: Low plasma levels of sRAGE is a potential biomarker for the risk of AS and may reflect the neurological severity of the condition, especially in subjects without identifiable conventional risk factors.
Alzheimer Disease ; Coronary Artery Disease ; Glycosylation End Products, Advanced ; Humans ; Hypercholesterolemia ; Hypertension ; Odds Ratio ; Plasma ; Risk Factors ; Stroke

PURPOSE: Diabetes changes the properties of collagen in our body tissue, increasing cross-linked collagen via nonenzymatic glycosylation and accumulation of advanced glycosylation end products. Glucose-derived cross-linked collagen formation may contribute to the development of chronic diabetic complications such as decreasing the compliance of tissue. Aminoguanidine, a hydrazine compound, prevent formation of glucose-derived collagen cross-linking. We studied the change of the properties of collagen in the corpus cavernosum by diabetes and the effects of insulin and aminoguanidine. MATERIALS AND METHODS: Diabetes was induced in male Sprague-Dawley rat and maintained for 12 weeks. Rats were divided into four groups: 1) control, 2) diabetics, 3) diabetics treated with insulin, 4) diabetics treated with aminoguanidine. Concentration of collagen in cavernosal tissue was measured by hydroxyproline content and expressed as hydroxyproline (micro gram) / dried defatted tissue (mg). The characteristic autofluorescence of glycosylated connective tissues of penile tissue was used to quantitate advanced glycosylation end products. RESULTS: The content of collagen in cavernosal tissue was not significantly different among experimental groups. Cross-linked collagen expressed as fluorescence (U/micro gram hydroxyproline) was increased in diabetic group (61.6+/-5.1) compared to control group (24.1+/-3.2) and it was decreased in both insulin-treated group (36.9+/-7.4) and aminoguanidine-treated group (37.9+/-5.8) compared to diabetic group. CONCLUSIONS: Our studies revealed that the properties of collagen in corpus cavernosum was changed by diabetes and that aminoguanidine as well as insulin prevented the diabetes-induced crossed linked collagen formation.
Animals ; Collagen* ; Compliance ; Connective Tissue ; Diabetes Complications ; Diabetes Mellitus ; Fluorescence ; Glycosylation ; Glycosylation End Products, Advanced ; Humans ; Hydroxyproline ; Insulin* ; Male ; Rats* ; Rats, Sprague-Dawley

BACKGROUND AND PURPOSE: The receptor for advanced glycation end products (RAGE) may contribute to the development of diabetic neuropathy. To assess its relevance in humans, this study examined the expression of RAGE in the skin biopsy samples of patients with diabetes mellitus, and investigated its correlation with intraepidermal nerve-fiber density (IENFD) and clinical measures of neuropathy severity. METHODS: Forty-four patients who either had type 2 diabetes or were prediabetes underwent clinical evaluation and a 3-mm skin punch biopsy. The clinical severity of their neuropathy was assessed using the Michigan Diabetic Neuropathy Score. IENFD was measured along with immunohistochemical staining for RAGE in 29 skin biopsy samples. The expression of RAGE was also quantified by real-time reverse-transcription PCR in the remaining 15 patients. RESULTS: RAGE was localized mostly in the dermal and subcutaneous vascular endothelia. The staining was more intense in patients with a lower IENFD (p=0.004). The quantity of RAGE mRNA was significantly higher in patients with severe neuropathy than in those with no or mild neuropathy (p=0.003). The up-regulation of RAGE was related to dyslipidemia and diabetic nephropathy. There was a trend toward decreased sural nerve action-potential amplitude and slowed peroneal motor-nerve conduction with increasing RAGE expression. CONCLUSIONS: The findings of this study demonstrate up-regulation of RAGE in skin biopsy samples from patients with diabetic neuropathy, supporting a pathogenic role of RAGE in the development of diabetic neuropathy.
Biopsy* ; Diabetes Mellitus ; Diabetic Nephropathies ; Diabetic Neuropathies* ; Dyslipidemias ; Glycosylation End Products, Advanced* ; Humans ; Michigan ; Polymerase Chain Reaction ; Prediabetic State ; Rage ; RNA, Messenger ; Skin* ; Sural Nerve ; Up-Regulation* ; Advanced Glycosylation End Product-Specific Receptor

BACKGROUND: Adenosine monophosphate-activated protein kinases (AMPKs), as a sensor of cellular energy status, have been known to play an important role in the pathophysiology of diabetes and its complications. Because AMPKs are known to be expressed in podocytes, it is possible that podocyte AMPKs could be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPKs in the pathological changes in podocytes induced by high-glucose (HG) and advanced glycosylation end products (AGEs) in diabetic proteinuria. METHODS: We prepared streptozotocin-induced diabetic renal tissues and cultured rat and mouse podocytes under diabetic conditions with AMPK-modulating agents. The changes in AMPKalpha were analyzed with confocal imaging and Western blotting under the following conditions: (1) normal glucose (5mM, =control); (2) HG (30mM); (3) AGE-added; or (4) HG plus AGE-added. RESULTS: The density of glomerularphospho-AMPKalpha in experimental diabetic nephropathy decreased as a function of the diabetic duration. Diabetic conditions including HG and AGE changed the localization of phospho-AMPKalpha from peripheral cytoplasm to internal cytoplasm and peri- and intranuclear areas in podocytes. HG reduced the AMPKalpha (Thr172) phosphorylation of rat podocytes, and similarly, AGEs reduced the AMPKalpha (Thr172) phosphorylation of mouse podocytes. The distributional and quantitative changes in phospho-AMPKalpha caused by diabetic conditions were preventable using AMPK activators, metformin, and 5-aminoimidazole-4-carboxamide-1beta-riboside. CONCLUSION: We suggest that diabetic conditions induce the relocation and suppression of podocyte AMPKalpha, which would be a suggestive mechanism in diabetic podocyte injury.
Adenosine* ; AMP-Activated Protein Kinases ; Animals ; Blotting, Western ; Cytoplasm ; Diabetic Nephropathies ; Glucose ; Glycosylation End Products, Advanced ; Metformin ; Mice ; Natural Resources ; Phosphorylation ; Podocytes* ; Protein Kinases* ; Proteinuria ; Rats