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Advanced glycation endproducts

Zhiyou Cai, Pei-Feng Qiao, Cheng-Qun Wan, Min Cai, Nan-Kai Zhou, Qin Li
The blood-brain barrier (BBB) is involved in the pathogenesis of Alzheimer's disease (AD). BBB is a highly selective semipermeable structural and chemical barrier which ensures a stable internal environment of the brain and prevents foreign objects invading the brain tissue. BBB dysfunction induces the failure of Aβ transport from brain to the peripheral circulation across the BBB. Especially, decreased levels of LRP-1 (low density lipoprotein receptor-related protein 1) and increased levels of RAGE (receptor for advanced glycation endproducts) at the BBB can cause the failure of Aβ transport...
May 16, 2018: Journal of Alzheimer's Disease: JAD
Suzan Wetzels, Kristiaan Wouters, Toshio Miyata, Jean L J M Scheijen, Jerome J A Hendriks, Casper G Schalkwijk, Tim Vanmierlo
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS). The immune response in MS patients leads to the infiltration of immune cells in the CNS and their subsequent activation. Immune cell activation induces a switch towards glycolysis. During glycolysis, the dicarbonyl product methylglyoxal (MGO) is produced. MGO is a glycating agent that can rapidly form advanced glycation endproducts (AGEs). In turn, AGEs are able to induce inflammatory responses. The glyoxalase system is the endogenous defense system of the body to reduce the burden of MGO thereby reducing AGE formation...
April 27, 2018: International Journal of Molecular Sciences
Sierra A Patterson, Gagan Deep, Tina E Brinkley
Exosomes are nanovesicles that participate in cell-to-cell communication and are secreted by a variety of cells including neurons. Recent studies suggest that neuronally-derived exosomes are detectable in plasma and that their contents likely reflect expression of various biomarkers in brain tissues. The receptor for advanced glycation endproducts (RAGE) has been implicated in the pathophysiology of Alzheimer's disease (AD) and is increased in brain regions affected by AD. The goal of our project was to determine whether RAGE is present in plasma exosomes, and specifically exosomes derived from neurons...
April 24, 2018: Biochemical and Biophysical Research Communications
K Kumar, Bandi Siva, V U M Sarma, Satish Mohabe, A Madhusudana Reddy, Joel Boustie, Ashok K Tiwari, N Rama Rao, K Suresh Babu
Comparative phytochemical analysis of five lichen species [Parmotrema tinctorum (Delise ex Nyl.) Hale, P. andinum (Mull. Arg.) Hale, P. praesorediosum (Nyl.) Hale, P. grayanum (Hue) Hale, P. austrosinense (Zahlbr.) Hale] of Parmotrema genus were performed using two complementary UPLC-MS systems. The first system consists of high resolution UPLC-QToF-MS/MS spectrometer and the second system consisted of UPLC-MS/MS in Multiple Reaction Monitoring (MRM) mode for quantitative analysis of major constituents in the selected lichen species...
April 19, 2018: Journal of Pharmaceutical and Biomedical Analysis
Yao-Wu Liu, Yun-Chao Hao, Ya-Jing Chen, Shen-Yuan Yin, Meng-Ya Zhang, Li Kong, Tao-Yun Wang
Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium...
April 23, 2018: Phytotherapy Research: PTR
Stephanie M Schindler, Matthew G Frank, Jessica L Annis, Steven F Maier, Andis Klegeris
Neuroinflammation is a common pathogenic mechanism for a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Microglia, the immune cells of the brain, contribute to the onset and progression of the neuroinflammation observed in these diseases. Microglia become activated and initiate an inflammatory response by interacting with a diverse set of molecules, including the group of endogenous proteins released upon cell damage, termed damage-associated molecular patterns (DAMPs)...
April 17, 2018: Molecular and Cellular Neurosciences
Andisheh Abedini, Julia Derk, Ann Marie Schmidt
Proteotoxicity plays a key role in many devastating human disorders, including Alzheimer's, Huntington's and Parkinson's diseases; type 2 diabetes; systemic amyloidosis; and cardiac dysfunction, to name a few. The cellular mechanisms of proteotoxicity in these disorders have been the focus of considerable research, but their role in prevalent and morbid disorders, such as diabetes, is less appreciated. There is a large body of literature on the impact of glucotoxicity and lipotoxicity on insulin-producing pancreatic β-cells, and there is increasing recognition that proteotoxicty plays a key role...
April 17, 2018: Protein Science: a Publication of the Protein Society
Hany M El-Bassossy, Thikryat Neamatallah, Khadijah S Balamash, Amani T Abushareb, Malcolm L Watson
BACKGROUND: Advanced glycation endproducts (AGEs) play a major role in the development of many vascular complications that are mediated by endothelial dysfunction. The present work aimed to investigate the mechanism by which AGEs impair vasodilation. METHODS: The effect of AGEs on vasodilation induced by acetylcholine or D NONOate was examined by incubating isolated rat aortae with different AGEs concentrations. ACh-induced nitric oxide generation was assessed using the fluorescent probe diaminofluorecein (DAF-FM)...
April 5, 2018: Biochemical and Biophysical Research Communications
Tobias Jost, Alexander Zipprich, Marcus A Glomb
Methylglyoxal is a major 1,2-dicarbonyl compound in vivo and leads to nonenzymatic protein modifications, known as advanced glycation endproducts. Especially long-lived proteins like collagen are prone to changes of the mechanical or biological function, respectively, by accumulation of Maillard-derived modifications. Specifically, the resulting nonenzymatic cross-link structures in parallel to the natural maturation process of collagen fibrils lead to complications with age or during disease. A novel lysine-lysine amide cross-link derived from methylglyoxal, 2,15-diamino-8-methyl-9-oxo-7,10-diaza-1,16-hexadecanedioic acid, named MOLA, was synthesized and identified in vitro and in vivo...
April 18, 2018: Journal of Agricultural and Food Chemistry
A H Burstein, M Sabbagh, R Andrews, C Valcarce, I Dunn, L Altstiel
Increasing evidence supports the role of the Receptor for Advanced Glycation Endproducts (RAGE) in the pathology of Alzheimer's disease. Azeliragon (TTP488) is an orally bioavailable small molecule inhibitor of RAGE in Phase 3 development as a potential treatment to slow disease progression in patients mild AD. Preclinical studies in animal models of AD (tgAPPSwedish/London) have shown azeliragon to decrease Aβ plaque deposition; reduce total Aβ brain concentration while increasing plasma Aβ levels; decreases sAPPβ while increasing sAPPα; reduce levels of inflammatory cytokines; and slow cognitive decline and improve cerebral blood flow...
2018: Journal of Prevention of Alzheimer's Disease
Liladhar Kashyap, Abdulhameed Alsaheel, Megan Ranck, Renee Gardner, John Maynard, Stuart A Chalew
Sickle cell disease (SCD) is associated with increased oxidative stress which potentially enhances generation of advanced glycation endproducts (AGEs). We estimated skin accumulation of AGEs in SCD patients and assessed their relationship with hemolysis and nephropathy. Skin intrinsic fluorescence (SIF), an estimate of AGEs, was assessed in African American patients with and without SCD. After skin excitation with light at 375, 405, and 420 nm, raw autofluorescence was adjusted using specific intrinsic corrections...
May 2018: Journal of Pediatric Hematology/oncology
Rajendra P Settem, Kiyonobu Honma, Mira Shankar, Miaomiao Li, Michael LaMonte, Ding Xu, Robert J Genco, Richard W Browne, Ashu Sharma
The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO) an electrophilic compound, which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, the concentrations of gingival-crevicular fluid MGO increase, and correlate with the levels of T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored...
March 23, 2018: Molecular Oral Microbiology
Masaki Kobayashi, Douglas W Zochodne
Diabetic polyneuropathy (DPN) continues to be generally considered as a "microvascular" complication of diabetes mellitus alongside nephropathy and retinopathy. The microvascular hypothesis, however, might be tempered by the concept that diabetes directly targets dorsal root ganglion sensory neurons. This neuron-specific concept, supported by accumulating evidence, might account for important features of DPN, such as its early sensory neuron degeneration. Diabetic sensory neurons develop neuronal atrophy alongside a series of messenger ribonucleic acid (RNA) changes related to declines in structural proteins, increases in heat shock protein, increases in the receptor for advanced glycation end-products, declines in growth factor signaling and other changes...
March 13, 2018: Journal of Diabetes Investigation
Stefano Menini, Carla Iacobini, Luisa de Latouliere, Isabella Manni, Vittoria Ionta, Claudia Blasetti Fantauzzi, Carlo Pesce, Paola Cappello, Francesco Novelli, Giulia Piaggio, Giuseppe Pugliese
Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation...
June 2018: Journal of Pathology
Attia Anwar, Provvidenza Maria Abruzzo, Sabah Pasha, Kashif Rajpoot, Alessandra Bolotta, Alessandro Ghezzo, Marina Marini, Annio Posar, Paola Visconti, Paul J Thornalley, Naila Rabbani
Background: Clinical chemistry tests for autism spectrum disorder (ASD) are currently unavailable. The aim of this study was to explore the diagnostic utility of proteotoxic biomarkers in plasma and urine, plasma protein glycation, oxidation, and nitration adducts, and related glycated, oxidized, and nitrated amino acids (free adducts), for the clinical diagnosis of ASD. Methods: Thirty-eight children with ASD (29 male, 9 female; age 7.6 ± 2.0 years) and 31 age-matched healthy controls (23 males, 8 females; 8...
2018: Molecular Autism
Peipei Sun, Ka-Wing Cheng, Yongjin He, Bin Liu, Xuemei Mao, Feng Chen
The formation and accumulation of advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of many chronic diseases, such as aging, Alzheimer' s disease, diabetes and diabetic complications. The present study was aimed to investigate the inhibitory effects of the extracts from nine microalgae on the formation of AGEs by using in vitro models and identify key antiglycation constituents of the microalgae. A BSA-glucose model with simulated physiological conditions was used to evaluate the inhibitory effect on total AGE formation...
March 1, 2018: Food & Function
Christos Spanos, Elaina M Maldonado, Ciarán P Fisher, Petchpailin Leenutaphong, Ernesto Oviedo-Orta, David Windridge, Francisco J Salguero, Alexandra Bermúdez-Fajardo, Mark E Weeks, Caroline Evans, Bernard M Corfe, Naila Rabbani, Paul J Thornalley, Michael H Miller, Huan Wang, John F Dillon, Alberto Quaglia, Anil Dhawan, Emer Fitzpatrick, J Bernadette Moore
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE-/- ) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS)...
2018: Proteome Science
Jer-An Lin, Chi-Hao Wu, Gow-Chin Yen
In the last 20 years, the effects of advanced glycation end products (AGEs) on health have received increasing attention. High AGE levels in the body correlate with the progression of many diseases, such as diabetes, cardiovascular disease, and some cancers. However, whether AGEs are a cause of these diseases or represent accompanying symptoms of these diseases still needs to be elucidated by more comprehensive research. Recently, many researchers have begun to investigate the effects of AGE intake-induced variations of gut microbiota on disease progression, which will further explain the impact of AGEs on health and open a new chapter in AGE research...
March 7, 2018: Journal of Agricultural and Food Chemistry
Christin Riedinger, Michael Mendler, Andrea Schlotterer, Thomas Fleming, Jürgen Okun, Hans-Peter Hammes, Stephan Herzig, Peter P Nawroth
The enzyme AICAR-transformylase/IMP cyclohydrolase (ATIC) catalyzes the last two steps of purine de novo synthesis. It metabolizes 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which is an AMP analogue, leading to activation of AMP-activated kinase (AMPK). We investigated whether the AICAR-ATIC pathway plays a role in the high glucose (HG)-mediated DNA damage response and AICAR-mediated AMPK activation, explaining the detrimental effects of glucose on neuronal damage and shortening of the lifespan...
March 30, 2018: Journal of Biological Chemistry
Alexander Klaus, Tim Baldensperger, Roman Fiedler, Matthias Girndt, Marcus A Glomb
In the present study, we investigated the role of transketolase (TK) in the modulation of glycolaldehyde driven Maillard reactions. In vitro experiments with recombinant human TK reduced glycolaldehyde and glyoxal induced carbonyl stress and thereby suppressed the formation of advanced glycation endproducts up to 70% due to the enzyme-catalyzed conversion of glycolaldehyde to erythrulose. This was further substantiated by the use of 13 C-labeled compounds. For the first time, glycolaldehyde and other sugars involved in the TK reaction were quantified in vivo and compared to nondiabetic uremic patients undergoing hemodialysis...
February 14, 2018: Journal of Agricultural and Food Chemistry
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