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Sample records for advanced glycation endproducts

  1. Advanced glycation endproducts in chronic heart failure

    NARCIS (Netherlands)

    Smit, Andries J.; Hartog, Jasper W. L.; Voors, Adriaan A.; van Veldhuisen, Dirk J.; Schleicher, E; Somoza,; Shieberle, P

    2008-01-01

    Advanced glycation endproducts (AGEs) have been proposed as factors involved in the development and progression of chronic heart failure (CHF). Cross-linking by AGEs results in vascular and myocardial stiffening, which are hallmarks in the pathogenesis of CHE Additionally, stimulation of receptors b

  2. Advanced glycation end-products inhibitors isolated from Schisandra grandiflora.

    Science.gov (United States)

    Poornima, B; Kumar, D Anand; Siva, Bandi; Venkanna, A; Vadaparthi, P R Rao; Kumar, K; Tiwari, Ashok K; Babu, K Suresh

    2016-01-01

    Free radicals scavenging and advanced glycation end-products (AGEs) inhibitory potentials in crude chloroform extract of Schisandra grandiflora were evaluated. Bioassay-guided isolation of the chloroform extract led to the identification of 24 compounds. Among the isolates, ( ± ) gomisin M1, arisantetralone C and D, macelignan, saurulignan B and SZ-MO displayed potent-free radical scavenging as well as AGEs inhibitory potentials. This is the first report identifying the presence of AGEs inhibitory activity and assigning AGEs inhibitory activity to these compounds. Therefore, our research finds new application of traditional medicinal plant S. grandiflora having capacity to reduce formation and accumulation of AGEs in diabetes.

  3. Advanced glycation endproducts in food and their effects on health

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Hedegaard, Rikke Susanne Vingborg; Andersen, Jeanette Marker;

    2013-01-01

    Advanced glycation endproducts (AGEs) form by Maillard-reactions after initial binding of aldehydes with amines or amides in heated foods or in living organisms. The mechanisms of formation may include ionic as well as oxidative and radical pathways. The reactions may proceed within proteins to f....... The current review points out several research needs in order to address important questions on AGEs in foods and health. © 2013 Elsevier Ltd.......Advanced glycation endproducts (AGEs) form by Maillard-reactions after initial binding of aldehydes with amines or amides in heated foods or in living organisms. The mechanisms of formation may include ionic as well as oxidative and radical pathways. The reactions may proceed within proteins...... to form high-molecular weight (HMW) AGEs or among small molecules to form low-molecular weight (LMW) AGEs. All free amino acids form AGEs, but lysine or arginine side chains dominate AGE formation within proteins. The analysis of AGEs in foods and body fluids is most often performed by ELISA or LC...

  4. Clinical relevance of advanced glycation endproducts for vascular surgery.

    Science.gov (United States)

    Meerwaldt, R; van der Vaart, M G; van Dam, G M; Tio, R A; Hillebrands, J-L; Smit, A J; Zeebregts, C J

    2008-08-01

    Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery.

  5. Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine.

    OpenAIRE

    Zimmerman, G A; Meistrell, M; Bloom, O.; Cockroft, K M; Bianchi, M.; Risucci, D; Broome, J.; Farmer, P; Cerami, A; Vlassara, H.

    1995-01-01

    Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Usin...

  6. Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats

    DEFF Research Database (Denmark)

    Oturai, P S; Christensen, M; Rolin, B;

    2000-01-01

    The accelerated formation of advanced glycation end-products (AGEs) due to elevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascular complications. The effects of a novel inhibitor of AGE formation, NNC39-0028 (2,3-diaminophenazine...... ameliorated by treatment with NNC39-0028, whereas PTB had no effect. Increased urinary albumin excretion (UAE) in diabetic rats was observed in serial measurements throughout the study period, and was not reduced by any treatment. Vascular dysfunction in the eye, measured as increased clearance of 125I...

  7. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    Science.gov (United States)

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-10-07

    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 "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  8. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    Directory of Open Access Journals (Sweden)

    Hillebrands Jan-Luuk

    2008-10-01

    Full Text Available Abstract 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 "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  9. A novel advanced glycation endproducts breaker restores cardiovascular dysfunctions in experimental diabetic rats

    Institute of Scientific and Technical Information of China (English)

    GangCHENG; Li-liWANG; Hong-yingLIU; HaoCUI; Ying-linCAO; SongLI

    2005-01-01

    AIM The formation of advanced glycation endproducts (AGEs) on connective tissue and matrix components leads to increases in collagen crosslinkingthat contributes to aortic and myocardial stiffness in normal aging and which occurs at an accelerated rate in diabetes. In this study, we examined the effects of a novel AGEs breaker, C36, on cardiovascular dysfunctions in experimental diabetic rats. METHODS and RESULTS Male Wiatar rats were made diabetic by i.p. injection of 70mg/kg streptozotocin. After 12 weeks of diabetes, the animals were randomly divided into 4 groups (n=8-11),

  10. Inhibition and breaking of advanced glycation end-products (AGEs) with bis-2-aminoimidazole derivatives

    Science.gov (United States)

    Richardson, Mike A.; Furlani, Robert E.; Podell, Brendan K.; Ackart, David F.; Haugen, Jessica D.; Melander, Roberta J.; Melander, Christian; Basaraba, Randall J.

    2015-01-01

    Advanced glycation end-products (AGEs), unregulated modifications to host macromolecules that occur as a result of metabolic dysregulation, play a role in many diabetes related complications, inflammation and aging, and may lead to increased cardiovascular risk. Small molecules that have the ability to inhibit AGE formation, and even break preformed AGEs have enormous therapeutic potential in the treatment of these disease states. We report the screening of a series of 2-aminoimidazloles for anti-AGE activity, and the identification of a bis-2-aminoimidazole lead compound that possesses superior AGE inhibition and breaking activity compared to the known AGE inhibitor aminoguanidine. PMID:26146419

  11. Screening system of blocking agents of the receptor for advanced glycation endproducts in cells using fluorescence.

    Science.gov (United States)

    Jung, Dong Ho; Kim, Young Sook; Kim, Jin Sook

    2012-01-01

    Activation of the receptor for advanced glycation endproducts (RAGE) triggers cellular responses implicated in the pathogenesis of diabetic complications; blockade of RAGE has been shown to inhibit the development of diabetic complications. To develop a screening system to identify novel disruptors of advanced glycation endproducts (AGE)-RAGE binding, we used an AGE-RAGE binding system in RAGE-overexpressing cells; test compounds were screened using this system. To construct human RAGE-overexpressing cells, mouse mesangial cells (MMCs) were stably transfected with the pcDNA-human RAGE (hRAGE) vector and selected under 1 mg/mL gentamicin (G418). RAGE expression in hRAGE-overexpressing MMCs was analyzed by Western blotting with specific RAGE antibody. To identify novel disruptors of AGE-RAGE binding, 50 single compounds and AGE-bovine serum albumin (BSA)-Alexa 488 (AGE-BSA labeled with Alexa 488) were treated to the hRAGE-overexpressing MMCs. Nonbinding AGE-BSA-Alexa 488 was washed and fluorescence measured by microtiter plate reader (excitation wavelength, 485 nm; emission wavelength, 528 nm). In hRAGE-overexpressing cells, only treatment with AGE-BSA-Alexa 488 significantly increased fluorescence intensity in a dose-dependent manner. Of 50 compounds tested, genistein disrupted AGE-RAGE binding in a dose-dependent manner. This AGE-RAGE binding system using AGE-BSA-Alexa 488 in hRAGE-overexpressing cells was suitable for screening of agents that disrupt AGE-hRAGE binding.

  12. A REVIEW ON ADVANCED GLYCATION END-PRODUCTS (AGE AND THEIR ROLE IN DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    KIRTESH RAUT

    2015-01-01

    Full Text Available A complex and heterogeneous group of compounds known as “Advanced Glycation End-products (AGE” have been associated with diabetes related complications. Till date it is not known if they are the cause or consequence of the complications observed. The chemistry of AGE formation and their patho-biochemistry particularly related to the diabetic microvascular complications of nephropathy, retinopathy and neuropathy also their role in the accelerated vasculopathy observed in diabetes are discussed. Also, the concept of carbonyl stress as a cause of AGE toxicity and the alterations in the concentrations of AGE in the body, particularly in relation to diabetes and its complications such as nephropathy are also mentioned and also along with age. We have also highlighted the problems relating to current methods of AGE detection and measurement which include the lack of a universally established method of detection or unit of measurement. A review of the agents used for the treatment of advanced glycation end-products accumulation is also mentioned.

  13. Advanced glycation end-products, anti-hypertensive treatment and diastolic function in patients with hypertension and diastolic dysfunction

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; van de Wal, Ruud M.; Schalkwijk, Casper G.; Miyata, Toshio; Jaarsma, Wybren; Plokker, H. W. Thijs; van Wijk, Leen M.; Smit, Andries J.; van Veldhuisen, Dirk J.; Voors, Adriaan A.

    2010-01-01

    Aims To investigate the relationship between advanced glycation end-products (AGEs) and diastolic function and the response to blood pressure treatment in patients with hypertension and diastolic dysfunction. Methods and results Data were analysed from 97 patients (aged 65 +/- 10 years, 36% male) wh

  14. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications.

    Science.gov (United States)

    Yan, Shi Fang; Ramasamy, Ravichandran; Schmidt, Ann Marie

    2008-05-01

    Many important biochemical mechanisms are activated in the presence of high levels of glucose, which occur in diabetes. Elevated levels of glucose accelerate the formation of advanced glycation end-products (AGEs). Via their chief signaling receptor-the AGE-specific receptor (commonly abbreviated as RAGE)-AGEs generate reactive oxygen species and activate inflammatory signaling cascades. Consequently, AGEs have key roles in the pathogenesis of diabetic complications. Two discoveries have advanced our knowledge of the roles of RAGE in inflammation. First, this receptor has multiple ligands and binds not only AGEs but also proinflammatory, calcium-binding S100 proteins (also known as calgranulins) and nuclear high mobility group protein box-1. Second, RAGE is expressed on T lymphocytes, monocytes and macrophages; RAGE expression on T lymphocytes is essential for effective priming of immune responses in vivo. In this Review, we chronicle roles for RAGE in the pathogenesis of diabetic complications and develop the hypothesis that, in addition to RAGE's central role in the inflammatory response, it is critically linked to the pathogenesis of types 1 and 2 diabetes. PMID:18332897

  15. Advanced Glycation End-Products Enhance Lung Cancer Cell Invasion and Migration

    Science.gov (United States)

    Hsia, Te-Chun; Yin, Mei-Chin; Mong, Mei-Chin

    2016-01-01

    Effects of carboxymethyllysine (CML) and pentosidine, two advanced glycation end-products (AGEs), upon invasion and migration in A549 and Calu-6 cells, two non-small cell lung cancer (NSCLC) cell lines were examined. CML or pentosidine at 1, 2, 4, 8 or 16 μmol/L were added into cells. Proliferation, invasion and migration were measured. CML or pentosidine at 4–16 μmol/L promoted invasion and migration in both cell lines, and increased the production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 and transforming growth factor-β1. CML or pentosidine at 2–16 μmol/L up-regulated the protein expression of AGE receptor, p47phox, intercellular adhesion molecule-1 and fibronectin in test NSCLC cells. Matrix metalloproteinase-2 protein expression in A549 and Calu-6 cells was increased by CML or pentosidine at 4–16 μmol/L. These two AGEs at 2–16 μmol/L enhanced nuclear factor κ-B (NF-κ B) p65 protein expression and p38 phosphorylation in A549 cells. However, CML or pentosidine at 4–16 μmol/L up-regulated NF-κB p65 and p-p38 protein expression in Calu-6 cells. These findings suggest that CML and pentosidine, by promoting the invasion, migration and production of associated factors, benefit NSCLC metastasis. PMID:27517907

  16. Chronic Spontaneous Urticaria Is Characterized by Lower Serum Advanced Glycation End-Products

    Directory of Open Access Journals (Sweden)

    Alicja Grzanka

    2014-01-01

    Full Text Available Background. Chronic spontaneous urticaria (CSU is associated with activation of acute phase response. On the other hand, it is known that systemic inflammation may lead to increased formation of advanced glycation end-products (AGEs, associated with pathogenesis of various diseases. Aim. We aim to test whether chronic inflammation manifested by activated acute phase response may provide a mechanism for increased serum AGEs concentration in CSU. Methods. Concentrations of AGEs were measured spectrofluorimetrically in serum of CSU patients and the healthy subjects. Results. Serum AGEs and albumin concentrations in CSU patients were significantly lower as compared with the healthy subjects. Serum CRP concentration was significantly higher in patients with CSU than in the controls. Significant positive correlation was observed between AGEs and albumin concentrations in the subjects. Conclusions. CSU is not associated with increased circulating AGEs concentrations, despite the enhanced systemic inflammatory response. Paradoxical decrease of serum AGEs concentrations is probably a reflection of lower concentration of “negative acute phase proteins” such as albumin.

  17. Cancer Malignancy Is Enhanced by Glyceraldehyde-Derived Advanced Glycation End-Products

    Directory of Open Access Journals (Sweden)

    Jun-Ichi Takino

    2010-01-01

    Full Text Available The receptor for advanced glycation end-products (RAGEs is associated with the malignancy of cancer. A recent study has suggested that glyceraldehyde-derived AGEs (Glycer-AGEs enhanced the malignancy of melanoma cells, but glucose-derived AGEs did not. However, the effects of Glycer-AGEs on other cancer cells remain poorly understood, and the molecular mechanisms behind the above-mentioned effect have not been clarified. The present paper aimed to examine the effect of Glycer-AGEs on cultured lung cancer A549 cells. RAGE was expressed in A549 cells. Glycer-AGEs significantly attenuated cell proliferation. Furthermore, Glycer-AGEs enhanced the migration capacity of the cells by activating Rac1 via ROS and also increased their invasion capacity. We demonstrated that Glycer-AGEs enhanced the migration and invasion of A549 cells rather than their proliferation. These results suggest that Glycer-AGEs play a critical role in the malignancy of cancer rather than its proliferation and are potential targets for therapeutic intervention.

  18. Influence of tonifying kidney recipe on advanced glycation endproducts and lipid peroxidation in ova riectomized rats

    Institute of Scientific and Technical Information of China (English)

    Yuefen Wang; Chang'an Zhao; Li Guo; En Li

    2008-01-01

    BACKGROUND:Previous studies have demonstrated that reduced estrogen levels may accelerate the formation of advanced glycation endproducts(AGE)in brain tissue,raise the concentration of lipid peroxidation products in vivo,and speed up deterioration of learning and memory.A tonifying kidney recipe is hypothesized to improve the ability of learning and memory in ovariectomized rats by downregulating AGE and lipid peroxidation products.OBJECTIVE:To simulate a postmenopausal state,bilateral ovariectomy (OVX)was performed in rats,and the effects of tonifying kidney recipe(TKR)on AGE and lipid peroxidation in the rat cerebral cortex,hippocampus,and blood serum levels was measured.In addition,the effects on learning and memory were evaluated,and the effect of AGE-specific inhibitor aminoguanidine(AG)was compared with TKR.DESIGN,TIME AND SETTING:A randomized,in vivo,control experiment was performed at the scientific research center(Provincial Key Laboratory)in the Fourth Hospital of Hebei Medical University (Shjiiazhuang,Hebei Province,China)from May 2005 to January 2007.MATERIALS:Forty healthy,adult,female,Sprague Dawley rats were used for this study.TKR was composed of prepared rehmannia rhizome,epimedium herb,desert-living cistanche,and Szechwan lovage rhizome,which were provided by Shijiazhuang Medical Materials Company(China).A TKR extraction was prepared for further use.AG was provided by Sigma (USA).Forty rats were randomly divided into four groups:sham,OVX,AG and TKR,with 10 rats in each group.METHODS:The rat ovaries were resected in the OVX,AG and TKR groups,whereas the same volume of fat was resected in the sham group.At four weeks after OVX,the AG group received 1% AG water solution by lavage;the TKR group was administrated by lavage once per day at a dose of 6.3 g (crude drug)/kg;OVX and sham groups received equal volumes of tap water.MAIN OUTCOME MEASURES:Learning and memory behavior of rats was tested in a Y-electric maze 16 weeks after the OVX procedure

  19. Advanced glycation endproducts in 35 types of seafood products consumed in eastern China

    Science.gov (United States)

    Wang, Jing; Li, Zhenxing; Pavase, Ramesh Tushar; Lin, Hong; Zou, Long; Wen, Jie; Lv, Liangtao

    2016-08-01

    Advanced glycation endproducts (AGEs) have been recognized as hazards in processed foods that can induce chronic diseases such as cardiovascular disease, diabetes, and diabetic nephropathy. In this study, we investigated the AGEs contents of 35 types of industrial seafood products that are consumed frequently in eastern China. Total fluorescent AGEs level and Nɛ-carboxymethyl-lysine (CML) content were evaluated by fluorescence spectrophotometry and gas chromatography-mass spectrometry (GC-MS), respectively. The level of total fluorescent AGEs in seafood samples ranged from 39.37 to 1178.3 AU, and was higher in canned and packaged instant aquatic products that were processed at high temperatures. The CML content in seafood samples ranged from 44.8 to 439.1 mg per kg dried sample, and was higher in roasted seafood samples. The total fluorescent AGEs and CML content increased when seafood underwent high-temperature processing, but did not show an obvious correlation. The present study suggested that commonly consumed seafood contains different levels of AGEs, and the seafood processed at high temperatures always displays a high level of either AGEs or CML.

  20. Decrease in fluorescence lifetime by glycation of collagen and its application in determining advanced glycation end-products in human dentin

    OpenAIRE

    Fukushima, Shuichiro; Shimizu, Masato; Miura, Jiro; Matsuda, Yusuke; Kubo, Mizuho; Hashimoto, Mamoru; Aoki, Takuya; Takeshige, Fumio; Araki, Tsutomu

    2015-01-01

    Advanced Glycation End-products (AGEs) are produced by the Maillard reaction, which causes cross-linking of collagen and results in changes in the mechanical properties of collagen tissues. Several types of AGE fluoresce, and measurement of this fluorescence is effective for determining the presence of AGEs. Because fluorescence intensity by steady-state fluorometry is affected by sample surface condition and light source, we focused on fluorescence lifetime measurement (FLM). We found that f...

  1. Inhibition of advanced glycation endproducts formation by Korean thistle,Cirsium maackii

    Institute of Scientific and Technical Information of China (English)

    Hyun Ah Jung; Jin Ju Park; Byung Sun Min; Hee Jin Jung; Md Nurul Islam; Jae Sue Choi

    2015-01-01

    Objective:To evaluate inhibitory potential of sevenKorean thistles against the advanced glycation endproducts(AGE) formation as well as to identify responsible compounds from the most active species.Methods:We used anin vitroAGE inhibition assay to evaluate the anti-diabetic complication potential of the methanol extracts of the selectedKorean thistles.Results:Among the sevenKorean thistles, the leaves ofCirsium maackii(C. maackii) exhibited the most significant inhibitory activity againstAGE formation.By means of bioassay-directed fractionation, a lignan, chlorogenic acid and14 flavonoids were isolated from the active ethyl acetate soluble fraction of a methanol extract fromC. maackii leaves.Luteolin and its5-O-glucoside have been previously isolated; however, a lignan and13 known compounds were isolated for the first time fromC. maackiileaves in this study.Most of the isolated compounds exhibited inhibitory activities against potentialAGE formation.Among them, cernuoside was shown to be the most potentAGE inhibitor with anIC50 value of21.21 μmol/L.Most importantly, two major flavonoids, luteolin and its5-O-glucoside, also significantly inhibitedAGE formation, withIC50 values of 36.33 and37.47 μmol/L, respectively.Structure activity relationship revealed that the presence of free3' and4' dihydroxyl group in flavonoids skeleton played an important role inAGE inhibition. Conclusions:These results indicate thatC. maackii andC. maackii-derived flavonoids might be explored further to develop therapeutic agents for the prevention of diabetic complications due to their significant inhibitory activity againstAGE formation.

  2. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    International Nuclear Information System (INIS)

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  3. C16, a novel advanced glycation endproduct breaker, restores cardiovascular dysfunction in experimental diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Gang CHENG; Li-li WANG; Wen-sheng QU; Long LONG; Hao CUI; Hong-ying LIU; Ying-lin CAO; Song LI

    2005-01-01

    Aim: Advanced glycation endproducts (AGE) have been implicated in the pathogenesis of diabetic complications, including diabetic cardiovascular dysfunction.3-[2-(4-Bromo-phenyl)- 1-methyl-2-oxo-ethyl]-4,5,6,7-tetrahydro-benzothiazol-3-ium bromide (C16), a novel AGE breaker, was investigated for its effects on the development of cardiovascular disease in diabetic rats. Methods: Rats that had streptozotocin-induced diabetes for 12 weeks were divided into groups receiving C16 or vehicle by gavage. Results: In hemodynamic studies of the left ventricle,C16 treatment (25 or 50 mg/kg) for 4 weeks resulted in a significant increase in left ventricular systolic pressure, +dp/dtmax, and -dp/dtmax as compared with vehicletreated diabetic rats. Furthermore, in hemodynamic studies of the cardiovascular system, C16 (12.5, 25, or 50 mg/kg) treatment for 4 weeks resulted in a dosedependent and significant increase in cardiac output, a reduction of total peripheral resistance, and an increase in systemic arterial compliance when compared with vehicle-treated diabetic rats. Biochemical studies showed that C16 treatment also resulted in a significant decrease in immunoglobulin G-red blood cell surface crosslink content and an increase in collagen solubility. Morphological and immunohistochemical examinations indicated that C 16 was able to prevent increases of the collagen type Ⅲ/Ⅰ ratio in the aorta and decrease the accumulation of AGE in the aorta. Conclusion: C16 has the ability to reduce AGE accumulation in tissues in vivo, and can restore diabetes-associated cardiovascular disorders in rats. This provides a potential therapeutic approach for cardiovascular disease associated with diabetes and aging in humans.

  4. Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel

    Directory of Open Access Journals (Sweden)

    Qiushi Wang

    2015-01-01

    Full Text Available Advanced glycation end-products (AGEs are complex and heterogeneous compounds implicated in diabetes. Sodium reabsorption through the epithelial sodium channel (ENaC at the distal nephron plays an important role in diabetic hypertension. Here, we report that H2S antagonizes AGEs-induced ENaC activation in A6 cells. ENaC open probability (PO in A6 cells was significantly increased by exogenous AGEs and that this AGEs-induced ENaC activity was abolished by NaHS (a donor of H2S and TEMPOL. Incubating A6 cells with the catalase inhibitor 3-aminotriazole (3-AT mimicked the effects of AGEs on ENaC activity, but did not induce any additive effect. We found that the expression levels of catalase were significantly reduced by AGEs and both AGEs and 3-AT facilitated ROS uptake in A6 cells, which were significantly inhibited by NaHS. The specific PTEN and PI3K inhibitors, BPV(pic  and LY294002, influence ENaC activity in AGEs-pretreated A6 cells. Moreover, after removal of AGEs from AGEs-pretreated A6 cells for 72 hours, ENaC PO remained at a high level, suggesting that an AGEs-related “metabolic memory” may be involved in sodium homeostasis. Our data, for the first time, show that H2S prevents AGEs-induced ENaC activation by targeting the ROS/PI3K/PTEN pathway.

  5. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

    OpenAIRE

    Šoupal, J.; G. Loni Ekali; Prázný, M.; Kalousová, M; Kvasnička, J.; L. Landová; Zima, T.; Škrha, J.

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.3...

  6. Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Ying Xing; Jinting He; Weidong Yu; Lingling Hou; Jiajun Chen

    2012-01-01

    A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

  7. Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

    NARCIS (Netherlands)

    de Groot, Lodewijk; Hinkema, Helmy; Westra, Johanna; Smit, Andries J.; Kallenberg, Cees G. M.; Bijl, Marc; Posthumus, Marcel D.

    2011-01-01

    Introduction: Advanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are incr

  8. Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; de Vries, Aiko P. J.; Bakker, Stephan J. L.; Graaff, Reindert; van Son, Willem J.; van der Heide, Jaap J. Homan; Gans, Reinold O. B.; Wolffenbuttel, Bruce H. R.; de Jong, Paul E.; Smit, Andries J.

    2006-01-01

    Background. Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplan

  9. Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts : An overview of current clinical studies, evidence, and limitations

    NARCIS (Netherlands)

    Mulder, Douwe J.; Van de Water, Tara; Lutgers, Helen L.; Graaff, Reindert; Gans, Rijk O.; Zijlstra, Felix; Smit, Andries J.

    2006-01-01

    Background: Advanced glycation endproducts (AGES) predict long-term complications in age-related diseases. However, there are no clinically applicable markers for measuring AGES in vivo. Methods: We have recently introduced the AGE-Reader (DiagnOptics B.V., Groningen, The Netherlands) to noninvasive

  10. The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals: a randomized factorial design trial.

    NARCIS (Netherlands)

    Oudegeest-Sander, M.H.; Olde Rikkert, M.G.M.; Smits, P.; Thijssen, D.H.J.; Dijk, A.P.J. van; Levine, B.D.; Hopman, M.T.E.

    2013-01-01

    Aging leads to accumulation of irreversible advanced glycation end-products (AGEs), contributing to vascular stiffening and endothelial dysfunction. When combined with the AGE-crosslink breaker Alagebrium, exercise training reverses cardiovascular aging in experimental animals. This study is the fir

  11. Advanced glycation end-product expression is upregulatedin the gastrointestinal tract of type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM: To investigate changes in advanced glycation endproducts (AGEs) and their receptor (RAGE) expressionin the gastrointestinal (GI) tract in type 2 diabetic rats.METHODS: Eight inherited type 2 diabetic rats Goto-Kakizak (GK) and ten age-matched normal rats wereused in the study. From 18 wk of age, the body weightand blood glucose were measured every week and 2wk respectively. When the rats reached 32 wk, twocentimetersegments of esophagus, duodenum,jejunum, ileum, and colon were excised and the wetweight was measured. The segments were fixedin 10% formalin, embedded in paraffin and fivemicron sections were cut. The layer thickness wasmeasured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected byimmunohistochemistry staining and image analysis wasdone using Sigmascan Pro 4.0 image analysis software.RESULTS: The blood glucose concentration (mmol/L)at 18 wk age was highest in the GK group (8.88 ±1.87 vs 6.90 ± 0.43, P 〈 0.001), a difference thatcontinued to exist until the end of the experiment.The wet weight per unit length (mg/cm) increased inesophagus, jejunum and colon from the normal to theGK group (60.64 ± 9.96 vs 68.56 ± 11.69, P 〈 0.05 foresophagus; 87.01 ± 9.35 vs 105.29 ± 15.45, P 〈 0.01for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90, P 〈 0.05for colon). Histologically, the layer thickness of the GI tract was higher for esophagus, jejunum and colon inthe GK group [full thickness (μm): 575.37 ± 69.22 vs753.20 ± 150.41, P 〈 0.01 for esophagus; 813.51 ±44.44 vs 884.81 ± 45.31, P 〈 0.05 for jejunum; 467.12± 65.92 vs 572.26 ± 93.60, P 〈 0.05 for colon]. Inesophagus, the AGE and RAGE mainly distributed instriated muscle cells and squamous epithelial cells. TheAGE distribution was much stronger in the GK groupcompared to the normal group both in the striatedmuscle layer and mucosa layer

  12. Role of advanced glycation endproducts and potential therapeutic interventions in dialysis patients.

    Science.gov (United States)

    Mallipattu, Sandeep K; He, John C; Uribarri, Jaime

    2012-01-01

    It has been nearly 100 years since the first published report of advanced glycation end products (AGEs) by the French chemist Maillard. Since then, our understanding of AGEs in diseased states has dramatically changed. Especially in the last 25 years, AGEs have been implicated in complications related to aging, neurodegenerative diseases, diabetes, and chronic kidney disease. Although AGE formation has been well characterized by both in vitro and in vivo studies, few prospective human studies exist demonstrating the role of AGEs in patients on chronic renal replacement therapy. As the prevalence of end-stage renal disease (ESRD) in the United States rises, it is essential to identify therapeutic strategies that either delay progression to ESRD or improve morbidity and mortality in this population. This article reviews the role of AGEs, especially those of dietary origin, in ESRD patients as well as potential therapeutic anti-AGE strategies in this population. PMID:22548330

  13. Advanced glycation End-products (AGEs): an emerging concern for processed food industries.

    Science.gov (United States)

    Sharma, Chetan; Kaur, Amarjeet; Thind, S S; Singh, Baljit; Raina, Shiveta

    2015-12-01

    The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). The chemistry of the AGEs formation, absorption and bioavailability and their patho-biochemistry particularly in relation to different complications like diabetes and ageing discussed. The concept of AGEs receptor - RAGE is mentioned. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Different methods of detection and quantification along with types of agents used for the treatment of AGEs are reviewed. Generally, ELISA or LC-MS methods are used for analysis of foods and body fluids, however lack of universally established method highlighted. The inhibitory effect of bioactive components on AGEs by trapping variety of chemical moieties discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

  14. Effect of advanced glycation end-products on cell proliferation and cell death.

    Science.gov (United States)

    Peterszegi, G; Molinari, J; Ravelojaona, V; Robert, L

    2006-09-01

    The effect of advanced glycation end products (AGE-s) was studied on the proliferation and cell death of human skin fibroblasts in culture. Several AGE-products were prepared from proteins, a peptide and amino acids, using Glucose or Fructose, with or without Fe2+. The AGE preparations increased cell death at the 7th day, after only 72 hours of incubation. Some of these glycation products modified also proliferation. This effect of AGE-s was even maintained without these products in fresh medium for a second period of incubation up to 10 days from the start of the experiment. In order to explore the role of AGE-receptors, especially of AGE-receptor and of growth factor receptors (fibroblast and epidermal growth factors receptors), antibodies to these receptors were added to cell cultures and their effect on both cell death and proliferation were determined as for the AGE-s. These anti-receptor antibodies imitated to some extent the results obtained with AGE-s, producing increase of cell death and proliferation, followed above a certain concentration of antibodies by a decrease and a new increase or plateau. This might correspond to the internalization of the receptors followed by a re-expression on the cell membrane. The role of receptor-mediated Reactive Oxygen Species-production was also explored using scavengers: N-acetyl-cysteine (NAC), L-Carnosine, superoxide dismutase (SOD) and Catalase. Several of these scavengers decreased cell death, suggesting that Reactive Oxygen Species-production is partially involved in the observed phenomena. PMID:16919894

  15. Receptor for Advanced Glycation End-Products Signaling Interferes with the Vascular Smooth Muscle Cell Contractile Phenotype and Function.

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    Elie Simard

    Full Text Available Increased blood glucose concentrations promote reactions between glucose and proteins to form advanced glycation end-products (AGE. Circulating AGE in the blood plasma can activate the receptor for advanced end-products (RAGE, which is present on both endothelial and vascular smooth muscle cells (VSMC. RAGE exhibits a complex signaling that involves small G-proteins and mitogen activated protein kinases (MAPK, which lead to increased nuclear factor kappa B (NF-κB activity. While RAGE signaling has been previously addressed in endothelial cells, little is known regarding its impact on the function of VSMC. Therefore, we hypothesized that RAGE signaling leads to alterations in the mechanical and functional properties of VSMC, which could contribute to complications associated with diabetes. We demonstrated that RAGE is expressed and functional in the A7r5 VSMC model, and its activation by AGE significantly increased NF-κB activity, which is known to interfere with the contractile phenotype of VSMC. The protein levels of the contraction-related transcription factor myocardin were also decreased by RAGE activation with a concomitant decrease in the mRNA and protein levels of transgelin (SM-22α, a regulator of VSMC contraction. Interestingly, we demonstrated that RAGE activation increased the overall cell rigidity, an effect that can be related to an increase in myosin activity. Finally, although RAGE stimulation amplified calcium signaling and slightly myosin activity in VSMC challenged with vasopressin, their contractile capacity was negatively affected. Overall, RAGE activation in VSMC could represent a keystone in the development of vascular diseases associated with diabetes by interfering with the contractile phenotype of VSMC through the modification of their mechanical and functional properties.

  16. Anti-Advanced glycation end-product and free radical scavenging activity of plants from the yucatecan flora

    Directory of Open Access Journals (Sweden)

    Wendy del C Dzib-Guerra

    2016-01-01

    Full Text Available Background: Formation and accumulation of advanced glycation end-products (AGE is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities. Materials and Methods: ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively. Results: the root extract of C. fistula (IC50= 0.1 mg/mL and the leaf extract of P. auritum (IC50= 0.35 mg/mL presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. <65Conclusions: the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism.

  17. Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?

    Science.gov (United States)

    Zhuang, Aowen; Forbes, Josephine M

    2016-08-01

    Diabetic patients are postulated to be in a perpetual state of oxidative stress and inflammation at sites where chronic complications occur. The accumulation of AGEs derived from both endogenous and exogenous sources (such as the diet) have been implicated in the development and progression of diabetic complications, particularly nephropathy. There has been some interest in investigating the potential for reducing the AGE burden in chronic disease, through the action of AGE "clearance" receptors, such as the advanced glycation end-product receptor 1 (AGE-R1). Reducing the burden of AGEs has been linked to attenuation of inflammation, slower progression of diabetic complications (in particular vascular and renal complications) and has been shown to extend lifespan. To date, however, there have been no direct investigations into whether AGE-R1 has any role in modulating normal kidney function, or specifically during the development and progression of diabetes. This mini-review will focus on the recent advances in knowledge around the mechanistic function of AGE-R1 and the implications of this for the pathogenesis of diabetic kidney disease. PMID:27270766

  18. Immunological evidence that non-carboxymethyllysine advanced glycation end-products are produced from short chain sugars and dicarbonyl compounds in vivo.

    OpenAIRE

    Takeuchi, M; Makita, Z; Bucala, R; Suzuki, T.; Koike, T.; Kameda, Y

    2000-01-01

    BACKGROUND: The Maillard reaction that leads to the formation of advanced glycation end-products (AGE) plays an important role in the pathogenesis of angiopathy in diabetic patients and in the aging process. Recently, it was proposed that AGE were not only created by glucose, but also by dicarbonyl compounds derived from the Maillard reaction, autoxidation of sugars and other metabolic pathways of glucose. In this study, we developed four types of non-carboxymethyllysine (CML) anti-AGE antibo...

  19. Identifizierung von Advanced glycated Endproducts im Speichel von Patienten mit Diabetes mellitus und deren Bedeutung für die Entwicklung von Parodontopathien

    OpenAIRE

    Montag, Susanne

    2010-01-01

    The main risk factors to develop a chronic peridontitis are an inadequate oral hygiene, smoking and diabetes mellitus. An increased oxidative stress and advanced glycated endproducts (AGE) are frequent reasons for side effects and complication in patients with diabetes mellitus. These include cardiovascular komplikcations e.g. vascular complications, vascular heart failure, diabetic nephropathy, and diabetic neuropathy. At present it is not known if the oxidative stress of the AGEs influences...

  20. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    Science.gov (United States)

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID:27672297

  1. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    Science.gov (United States)

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

  2. Advanced glycation end-products in the peritoneal fluid and in the peritoneal membrane of continuous ambulant peritoneal dialysis patients.

    Science.gov (United States)

    Mahiout, A; Ehlerding, G; Brunkhorst, R

    1996-01-01

    In patients on continuous ambulant peritoneal dialysis (CAPD) treatment, the peritoneal membrane is continuously exposed to the high glucose concentration contained in the dialysate. This may lead to the local generation of advanced glycation end-products (AGEs). To test this hypothesis we evaluated the plasma and dialysate AGE concentrations in five CAPD patients. The dialysate was measured after a 1 h and after a 12 h dwell time. Additionally, in two patients an immunohistochemical investigation of the peritoneal membrane for AGE was performed. For the determination of AGE an ELISA using a polyclonal antibody against AGE bovine serum albumin was used; the immunohistochemical staining was performed using the streptavidin-biotin complex method. We found only low concentrations of AGE in the dialysate after a 1 h dwell time; after 12 h, however, the dialysate AGE was even greater than the plasma concentration. In both peritoneal specimens we found positive staining for AGE in the interstitium of the mesothelial layer. The dialysate AGE contained a high proportion of high-molecular-weight AGE proteins and low-molecular-weight AGE was found to be in the same concentration range as the total serum AGE. We conclude that there is local generation of AGE in the peritoneal membrane and a 'washing out' of AGE from the peritoneal membrane during longer dwell times. We speculate that the accumulation of AGE might lead to some of the functional and morphological alterations observed after long-term CAPD.

  3. Decreased level of endogenous secretory receptor for advanced glycation end-products in diabetes with concomitant hyperlipidemia.

    Science.gov (United States)

    Turk, Z; Ljubić, S; Boras, J

    2014-01-01

    Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE) acts as decoy for AGEs. The AGE-to-esRAGE ratio was hypothesized to be implicated in diabetic vasculopathy. We investigated an association of esRAGE and methylglyoxal-adducts serum level, as well as AGE-to-esRAGE ratio in subpopulation of diabetic patients with or without concomitant hyperlipidemia and macrovascular disease in history. In diabetes with concomitant hyperlipidemia esRAGE was significantly decreased compared to hyperlipidemia with normal glucose metabolism (0.306+/-0.2 vs. 0.367+/-0.1; p=0.019) or diabetes alone (0.306+/-0.2 vs. 0.404+/-0.1; p=0.004). High AGE/esRAGE ratio, found in diabetic patients with hyperlipidemia, pointed to increased production of AGEs and low expression of esRAGE. In multivariable analysis adjusted for several confounding factors, increased AGE/esRAGE ratio was recognized as a high risk for vascular disease outcomes.

  4. Phenolics from Garcinia mangostana Inhibit Advanced Glycation Endproducts Formation: Effect on Amadori Products, Cross-Linked Structures and Protein Thiols

    Directory of Open Access Journals (Sweden)

    Hossam M. Abdallah

    2016-02-01

    Full Text Available Accumulation of Advanced Glycation Endproducts (AGEs in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG as a positive control. Including G. mangostana total methanol extract (GMT in the reaction mixture of bovine serum albumin (BSA and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (1, aromadendrin-8-C-glucopyranoside (2, epicatechin (3, and 2,3′,4,5′,6-pentahydroxybenzophenone (4. All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound 3 (epicatechin was found to be the most potent. In search for the level of action, addition of GMT, and compounds 2–4 inhibited fructosamine (Amadori product and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (3 to reaction mixture increased protein thiol in both glucose and ribose while compounds 1, 2 and 4 only increased thiol in case of ribose. In conclusion, phenolic compounds 1–4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol.

  5. Phenolics from Garcinia mangostana Inhibit Advanced Glycation Endproducts Formation: Effect on Amadori Products, Cross-Linked Structures and Protein Thiols.

    Science.gov (United States)

    Abdallah, Hossam M; El-Bassossy, Hany; Mohamed, Gamal A; El-Halawany, Ali M; Alshali, Khalid Z; Banjar, Zainy M

    2016-01-01

    Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG) as a positive control. Including G. mangostana total methanol extract (GMT) in the reaction mixture of bovine serum albumin (BSA) and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (1), aromadendrin-8-C-glucopyranoside (2), epicatechin (3), and 2,3',4,5',6-pentahydroxybenzophenone (4). All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound 3 (epicatechin) was found to be the most potent. In search for the level of action, addition of GMT, and compounds 2-4 inhibited fructosamine (Amadori product) and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (3) to reaction mixture increased protein thiol in both glucose and ribose while compounds 1, 2 and 4 only increased thiol in case of ribose. In conclusion, phenolic compounds 1-4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol. PMID:26907243

  6. Anti-Advanced Glycation End-product and Free Radical Scavenging Activity of Plants from the Yucatecan Flora

    Science.gov (United States)

    Dzib-Guerra, Wendy del C.; Escalante-Erosa, Fabiola; García-Sosa, Karlina; Derbré, Séverine; Blanchard, Patricia; Richomme, Pascal; Peña-Rodríguez, Luis M.

    2016-01-01

    Background: Formation and accumulation of advanced glycation end-products (AGE) is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities. Materials and Methods: ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively. Results: the root extract of C. fistula (IC50= 0.1 mg/mL) and the leaf extract of P. auritum (IC50= 0.35 mg/mL) presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. Conclusions: the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism. SUMMARY Ethanolic extracts from nine plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine were tested for their anti-AGE and free radical

  7. Relationship between advanced glycation end-products with the severity of chronic heart failure in 85 patients

    Directory of Open Access Journals (Sweden)

    Amir Farhang Zand Parsa

    2013-12-01

    Full Text Available Background: Advanced glycation end-products (AGEs came up with the recent researches regarding new biomarkers for the diagnosis of heart failure. AGEs are the end products of non-enzymatic glycation and oxidation of proteins, lipids and nucleotides during Maillard biochemical reaction. Although it has been known that AGEs have a role in the pathogenesis of chronic heart failure (CHF, information regarding its role and its pathogenetic mechanism is very limited. The aim of this study was to find any relationship between AGEs with the etiology and severity of chronic heart failure.Methods: This study is a prospective cross sectional study that enrolled 85 patients with chronic heart failure. Measurement of left ventricle ejection fraction (LVEF was done by echocardiography. Blood samples were collected for measuring AGEs just before or after echocardiography assessment (in the same session. Measurement of AGEs was done by the enzyme-linked immunosorbent assay (ELISA method. The relationship between AGEs with the severity of CHF and as well as the etiology of CHF were evaluated via SPSS-15.Results: Of 85 patients 48 (56.5% patients were male and 37 (43.5% were female; Mean±SD of their ages was 55.8±13.4 years old (ranges from 27 to 84 years. Correlation coefficient between LVEF and AGEs was 0.269 (P=0.013. Mean of AGEs in patients with and without ischemic etiology of their heart failure were 16.8±9.8µg/ml and 11.6±7.3 µg/ml, respectively. Although trend was in favor of ischemic heart failure, the difference between two groups was not statistically significant (P= 0.141.Conclusion: According to this study the rate of AGES could be helpful in the diagnosis and assessment of severity of CHF. Based on our findings, higher blood levels of AGEs in the ischemic CHF cases, also it could be concluded that in the future this marker may be used for etiologic differentiation of heart failure syndrome.

  8. Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification

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    Sayo Koike

    2016-09-01

    Full Text Available Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD. To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs stimulated calcium deposition in vascular smooth muscle cells (VSMCs through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5 was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA. Apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD(PH oxidase components including Nox4 and p22phox, and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22phox. Double knockdown of Nox4 and p22phox showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD(PH oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD.

  9. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

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    J. Škrha

    2013-01-01

    Full Text Available The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE in patients with diabetes. Skin autofluorescence (AF assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/ and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P<0.0001. Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r=0.37, P<0.02 and r=0.60, P<0.0001, but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R2=0.38. Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  10. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    Science.gov (United States)

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  11. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    Science.gov (United States)

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established. PMID:23671885

  12. Carboxymethyl lysine, an advanced glycation end-product, and incident diabetes: a case-cohort analysis of the ARIC Study

    Science.gov (United States)

    Luft, V. C.; Duncan, B. B.; Schmidt, M. I.; Chambless, L. E.; Pankow, J. S.; Hoogeveen, R. C.; Couper, D. J.; Heiss, G.

    2016-01-01

    Aims To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end-product (AGE), predict the development of diabetes in middle-age adults. Methods Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. Results In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually <0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, body mass index, waist-to-hip ratio, NEFA, oxidized LDL-cholesterol, glomerular filtration rate, smoking, an inflammation score, adiponectin, leptin, insulin, and glucose levels, was associated with increased risk of diabetes (HR=1.35; 95% CI 1.09 – 1.67, for each 100 ng/mL CML increment). Baseline glucose level and race each modified the association (p<0.05 for interaction), which was present only among those with impaired fasting glucose (≥5.6 mmol/l, HR=1.61, 95%CI 1.26 – 2.05) and among whites (HR=1.50, 95%CI 1.13 – 1.99). Conclusions Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in whites. These prospective findings suggest that AGE might play a role in the development of diabetes. PMID:26359784

  13. Expression of receptor for advanced glycation endproducts and nuclear factor κB in brain hippocampus of rat with chronic fluorosis

    Institute of Scientific and Technical Information of China (English)

    张凯琳

    2014-01-01

    Objective To investigate the expressions of receptor for advanced glycation endproducts(RAGE)and nuclear factorκB(NF-κB)in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male)fed with different contents of fluoride,control group with normal tap-water(<0.5 mg/L fluoride),

  14. Dietary advanced glycation endproducts

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe

    sensitivity and markers of inflammation and oxidative stress were found. In conclusion, results from this PhD thesis suggest that diets prepared by low heat may reduce risk markers for type 2 diabetes and cardiovascular disease. However, it can currently not be concluded that AGEs are responsible...... complications. A potential pathophysiological role of dietary AGEs in type 2 diabetes and cardiovascular disease has been discussed, as the contribution of dietary AGEs has been estimated to be larger than the amount of endogenously formed AGEs. Furthermore, the increased mortality associated with type 2...... diabetes and cardiovascular disease underlines the importance of identifying possible risk factors in the Western lifestyle. The overall aim of this thesis was to investigate if intake of dietary AGEs increases risk markers for type 2 diabetes and cardiovascular disease. In an acute meal study, effects...

  15. Advanced glycation end-products induce heparanase expression in endothelial cells by the receptor for advanced glycation end products and through activation of the FOXO4 transcription factor.

    Science.gov (United States)

    An, Xiao-Fei; Zhou, Lei; Jiang, Peng-Jun; Yan, Ming; Huang, Yu-Jun; Zhang, Su-Na; Niu, Yun-Fei; Ten, Shi-Chao; Yu, Jiang-Yi

    2011-08-01

    As an endo-β (1-4)-D: -glucuronidase, heparanase can specifically cleave carbohydrate chains of heparan sulfate (HS) and has been implicated in development of endothelial cells dsyfunction. The advanced glycation end products (AGEs) play a pivotal role in the pathology of diabetic complications. In the present study, we investigated the effect of AGE-bovine serum albumin (AGE-BSA) on heparanase expression in human microvascular endothelial cells (HMVECs) and the underlying molecular mechanisms. The results indicated that in vitro direct exposure of HMVECs to AGE-BSA (300, 1000, and 3000 μg/ml) could increase heparanase mRNA and protein expression in a dose and time-dependent manner. The effect of 1000 μg/ml AGE-BSA could be abolished by neutralization with antibody of the receptor for advanced glycation end products (RAGE). Moreover, pretreatment with inhibitors of nuclear factor-κB (NF-κB) or PI3-kinase did not affect heparanase expression induced by AGE-BSA. Nevertheless, small interference RNA (siRNA) for transcriptional factor FOXO4 could reduce the increase of heparanase expression in HMVECs induced by 1000 μg/ml AGE-BSA. These results suggest that AGEs could induce heparanase expression in HMVECs by RAGE and predominantly through activation of the FOXO4 transcription factor.

  16. Soluble Levels of Receptor for Advanced Glycation Endproducts (RAGE) and Progression of Atherosclerosis in Individuals Infected with Human Immunodeficiency Virus: ACTG NWCS 332.

    Science.gov (United States)

    Danoff, Ann; Kendall, Michelle A; Currier, Judith S; Kelesidis, Theodoros; Schmidt, Ann Marie; Aberg, Judith A

    2016-08-01

    Identification of biomarkers and/or mediators of cardiovascular disease (CVD) associated with HIV infection would be of diagnostic and therapeutic value. As soluble receptor for advanced glycation endproducts (sRAGE) and endogenous secretory (esRAGE) have been implicated in vascular complications in other settings, we investigated whether either soluble form of RAGE was associated with changes in carotid intima-media thickness (CIMT) in HIV-infected patients and HIV-uninfected controls. We found no differences in sRAGE, esRAGE, or CIMT among groups at study entry, or in yearly rates of change in sRAGE, esRAGE, or CIMT by HIV-serostatus (all p > 0.10). However, yearly rates of change in sRAGE (p = 0.07) and esRAGE (p mediator of CVD in HIV-infected persons. PMID:27216802

  17. Soluble Forms and Ligands of the Receptor for Advanced Glycation End-Products in Patients with Acute Respiratory Distress Syndrome: An Observational Prospective Study.

    Directory of Open Access Journals (Sweden)

    Matthieu Jabaudon

    Full Text Available The main soluble form of the receptor for advanced glycation end-products (sRAGE is elevated during acute respiratory distress syndrome (ARDS. However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS.30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE, high mobility group box-1 protein (HMGB1, S100A12 and advanced glycation end-products (AGEs were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography.ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels of esRAGE and AGEs, than controls. Baseline arterial sRAGE, HMGB1 and S100A12 were correlated with nonfocal ARDS (AUC 0.79, 0.65 and 0.63, respectively. Baseline arterial sRAGE, esRAGE, S100A12 and AGEs were associated with severity as assessed by PaO2/FiO2.This is the first kinetics study of levels of RAGE main isoforms and ligands during ARDS. Elevated sRAGE, HMGB1 and S100A12, with decreased esRAGE and AGEs, were found to distinguish patients with ARDS from those without. Our findings should prompt future studies aimed at elucidating RAGE/HMGB1/S100A12 axis involvement in ARDS.clinicaltrials.gov Identifier: NCT01270295.

  18. Inhibition of Advanced Glycation End-Product Formation and Antioxidant Activity by Extracts and Polyphenols from Scutellaria alpina L. and S. altissima L.

    Science.gov (United States)

    Grzegorczyk-Karolak, Izabela; Gołąb, Krzysztof; Gburek, Jakub; Wysokińska, Halina; Matkowski, Adam

    2016-01-01

    Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE) in vitro. S. alpina, which is richer in polyphenolic compounds, had strong antiglycation properties. These extracts demonstrated also high activity in the FRAP (ferric-reducing antioxidant power), antiradical (DPPH) and lipid peroxidation inhibition assays. Among the pure compounds, baicalin was the strongest glycation inhibitor (90.4% inhibition at 100 μg/mL), followed by luteolin (85.4%). Two other flavone glycosides had about half of this activity. Verbascoside was similar to the reference drug aminoguanidine (71.2% and 75.9%, respectively). The strong correlation observed between AGE inhibition and total flavonoid content indicated that flavonoids contribute significantly to antiglycation properties. A positive correlation was also observed between antiglycative and antioxidant activities. The studied skullcap species can be considered as a potential source of therapeutic agents for hyperglycemia-related disorders. PMID:27314314

  19. Inhibition of Advanced Glycation End-Product Formation and Antioxidant Activity by Extracts and Polyphenols from Scutellaria alpina L. and S. altissima L.

    Directory of Open Access Journals (Sweden)

    Izabela Grzegorczyk-Karolak

    2016-06-01

    Full Text Available Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE in vitro. S. alpina, which is richer in polyphenolic compounds, had strong antiglycation properties. These extracts demonstrated also high activity in the FRAP (ferric-reducing antioxidant power, antiradical (DPPH and lipid peroxidation inhibition assays. Among the pure compounds, baicalin was the strongest glycation inhibitor (90.4% inhibition at 100 μg/mL, followed by luteolin (85.4%. Two other flavone glycosides had about half of this activity. Verbascoside was similar to the reference drug aminoguanidine (71.2% and 75.9%, respectively. The strong correlation observed between AGE inhibition and total flavonoid content indicated that flavonoids contribute significantly to antiglycation properties. A positive correlation was also observed between antiglycative and antioxidant activities. The studied skullcap species can be considered as a potential source of therapeutic agents for hyperglycemia-related disorders.

  20. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP) and advanced glycation end-products (AGE, RAGE) in patients with ischemic heart disease and type 2 diabetes mellitus

    OpenAIRE

    Ekaterina Vladimirovna Ivannikova; Konstantin Vladimirovich Melkozerov; Viktor Yur'evich Kalashnikov; Sergey Anatol'evich Terekhin; Irina Vladimirovna Kononenko; Olga Mikhailovna Smirnova

    2013-01-01

    Aims. To evaluate plasma levels of transforming growth factor beta (TGFβ1), basic fibroblast growth factor (bFGF), markers for nonspecific inflammatory process (interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP)) and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD).Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standar...

  1. The effect of fibroblast growth factors and advanced glycation end-products on the intima-media complex thickness in patients with coronary heart disease and type 2 diabetes

    OpenAIRE

    Ekaterina Vladimirovna Ivannikova; Victor Yurievich Kalashnikov; Olga Mikhaylovna Smirnova; Alexander Borisovich Kuznetsov; Sergei Anatolievich Terekhin; Alexander Viktorovich Il'in

    2014-01-01

    ObjectiveTo determine the levels of fibroblast transforming growth factor (TGFβ1), basic fibroblast growth factor (β-FGF), markers of nonspecific inflammatory response (interleukin-6 (IL-6)), C-reactive protein (CRP), advanced glycation end-products (AGEs) and their receptors (RAGEs) and to study their effect on the intima-media complex (IMC) thickness in patients with coronary heart disease (CHD) and type 2 diabetes, depending on carbohydrate metabolism compensation.Materials and Methods37 p...

  2. Effect of Amaranthus on Advanced Glycation End-Products Induced Cytotoxicity and Proinflammatory Cytokine Gene Expression in SH-SY5Y Cells.

    Science.gov (United States)

    Amornrit, Warisa; Santiyanont, Rachana

    2015-01-01

    Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Advanced glycation end-products (AGEs) cause cell toxicity in the human neuronal cell line, SH-SY5Y, through an increase in oxidative stress, as shown by reducing cell viability and increasing cell toxicity in a dose-dependent manner. We found that preincubation of SH-SY5Y cells with either petroleum ether, dichloromethane or methanol extracts of A. lividus and A. tricolor dose-dependently attenuated the neuron toxicity caused by AGEs treatment. Moreover, the results showed that A. lividus and A. tricolor extracts significantly downregulated the gene expression of the pro-inflammatory cytokines, TNF-α, IL-1 and IL-6 genes in AGEs-induced cells. We concluded that A. lividus and A. tricolor extracts not only have a neuroprotective effect against AGEs toxicity, but also have anti-inflammatory activity by reducing pro-inflammatory cytokine gene expression. This suggests that Amaranthus may be useful for treating chronic inflammation associated with neurodegenerative disorders. PMID:26393562

  3. Effect of Amaranthus on Advanced Glycation End-Products Induced Cytotoxicity and Proinflammatory Cytokine Gene Expression in SH-SY5Y Cells

    Directory of Open Access Journals (Sweden)

    Warisa Amornrit

    2015-09-01

    Full Text Available Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Advanced glycation end-products (AGEs cause cell toxicity in the human neuronal cell line, SH-SY5Y, through an increase in oxidative stress, as shown by reducing cell viability and increasing cell toxicity in a dose-dependent manner. We found that preincubation of SH-SY5Y cells with either petroleum ether, dichloromethane or methanol extracts of A. lividus and A. tricolor dose-dependently attenuated the neuron toxicity caused by AGEs treatment. Moreover, the results showed that A. lividus and A. tricolor extracts significantly downregulated the gene expression of the pro-inflammatory cytokines, TNF-α, IL-1 and IL-6 genes in AGEs-induced cells. We concluded that A. lividus and A. tricolor extracts not only have a neuroprotective effect against AGEs toxicity, but also have anti-inflammatory activity by reducing pro-inflammatory cytokine gene expression. This suggests that Amaranthus may be useful for treating chronic inflammation associated with neurodegenerative disorders.

  4. The receptor for advanced glycation end-products (RAGE) plays a key role in the formation of nanotubes (NTs) between peritoneal mesothelial cells and in murine kidneys.

    Science.gov (United States)

    Ranzinger, Julia; Rustom, Amin; Heide, Danijela; Morath, Christian; Schemmer, Peter; Nawroth, Peter P; Zeier, Martin; Schwenger, Vedat

    2014-09-01

    The receptor for advanced glycation end-products (RAGE), a multiligand receptor of the immunoglobulin superfamily, takes part in various inflammatory processes. The role of this receptor in the context of intercellular communication, like nanotube (NT)-mediated interaction, is largely unknown. Here, we use cell cultures of human and murine peritoneal mesothelial cells as well as murine kidneys from wild-type and RAGE knockout mouse models to assess the role of RAGE in NT formation and function. We show that loss of RAGE function results in reduced NT numbers under physiological conditions and demonstrate the involvement of MAP kinase signaling in NT formation. Additionally, we show for the first time the existence of NTs in murine kidney tissue and confirm the correlation of RAGE expression and NT numbers. Under elevated oxidative stress conditions like renal ischemia or peritoneal dialysis, we demonstrate that RAGE absence does not prevent NT formation. Rather, increased NT numbers and attenuated kidney tissue damage could be observed, indicating that, depending on the predominant conditions, RAGE affects NT formation with implications for cellular communication.

  5. Effect of Moringa oleifera on advanced glycation end-product formation and lipid metabolism gene expression in HepG2 cells.

    Science.gov (United States)

    Sangkitikomol, W; Rocejanasaroj, A; Tencomnao, T

    2014-01-01

    In Thai traditional medicine, Moringa oleifera is used for the treatment of diabetes and hyperlipidemia. Oxidative stress plays a major role in the pathogenesis of many degenerative diseases, such as hyperlipidemia, diabetes mellitus, and cardiovascular disease. We evaluated the antioxidant effect of M. oleifera extract (MOE) for reduction of advanced glycation end-product (AGE) formation, cell viability, oxidative stress, and lipid metabolism gene expression in HepG2 cells. We found that the lyophilized form of MOE in 80% ethanol possessed mean (± SD) total antioxidant, polyphenolic, and flavonoid contents of 9307 ± 364 TE mM/kg dry mass, 218 ± 1 GE mM/kg dry mass, and 286 ± 12 QE mM/kg dry mass, determined using an oxygen radical absorbance capacity assay, a Folin Ciocalteu phenol assay, and a total flavonoids assay, respectively. Concentrations of 2.5-10.0 mg/mL MOE could inhibit AGE-formation by 10-45%, and 100-1000 mg/L MOE reduced intracellular oxidative stress (P < 0.05) in a dose-dependent manner in the DCFH-DA assay. However, MOE induced cytotoxicity at high doses (2000-3000 mg/L), as shown by the MTT assay. MOE significantly downregulated the mRNA expression of the HMG-CoAR, PPARα1, and PPARγ genes (P < 0.05). We concluded that M. oleifera could have benefits for human health by reducing oxidative stress and AGE formation. Moreover, M. oleifera may reduce cholesterol and lipid synthesis by suppression of HMG-CoAR, PPARα1, and PPARγ gene expression, thereby maintaining lipid homeostasis. PMID:24615037

  6. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    Energy Technology Data Exchange (ETDEWEB)

    Puddu, A., E-mail: alep100@hotmail.com [University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 16132 Genova (Italy); Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L. [University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 16132 Genova (Italy)

    2010-07-30

    Research highlights: {yields} GLP-1 prevents AGEs-induced cell death. {yields} GLP-1 prevents AGEs-induced oxidative stress. {yields} GLP-1 ameliorated AGEs-induced cell dysfunction. {yields} GLP-1 attenuates AGEs-induced RAGE increment. {yields} GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  7. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    International Nuclear Information System (INIS)

    Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  8. Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products.

    Science.gov (United States)

    Liu, Jhih-Syuan; Chuang, Tsung-Ju; Chen, Jui-Hung; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Lin, Tsung-Kun; Hsiao, Fone-Ching; Hung, Yi-Jen

    2015-08-01

    Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD. PMID:25666934

  9. Advanced glycation end-products induce apoptosis in pancreatic islet endothelial cells via NF-κB-activated cyclooxygenase-2/prostaglandin E2 up-regulation.

    Directory of Open Access Journals (Sweden)

    Kuo-Cheng Lan

    Full Text Available Microvascular complications eventually affect nearly all patients with diabetes. Advanced glycation end-products (AGEs resulting from hyperglycemia are a complex and heterogeneous group of compounds that accumulate in the plasma and tissues in diabetic patients. They are responsible for both endothelial dysfunction and diabetic vasculopathy. The aim of this study was to investigate the cytotoxicity of AGEs on pancreatic islet microvascular endothelial cells. The mechanism underlying the apoptotic effect of AGEs in pancreatic islet endothelial cell line MS1 was explored. The results showed that AGEs significantly decreased MS1 cell viability and induced MS1 cell apoptosis in a dose-dependent manner. AGEs dose-dependently increased the expressions of cleaved caspase-3, and cleaved poly (ADP-ribose polymerase in MS1 cells. Treatment of MS1 cells with AGEs also resulted in increased nuclear factor (NF-κB-p65 phosphorylation and cyclooxygenase (COX-2 expression. However, AGEs did not affect the expressions of endoplasmic reticulum (ER stress-related molecules in MS1 cells. Pretreatment with NS398 (a COX-2 inhibitor to inhibit prostaglandin E2 (PGE2 production reversed the induction of cleaved caspase-3, cleaved PARP, and MS1 cell viability. Moreover, AGEs significantly increased the receptor for AGEs (RAGE protein expression in MS1 cells, which could be reversed by RAGE neutralizing antibody. RAGE Neutralizing antibody could also reverse the induction of cleaved caspase-3 and cleaved PARP and decreased cell viability induced by AGEs. These results implicate the involvement of NF-κB-activated COX-2/PGE2 up-regulation in AGEs/RAGE-induced islet endothelial cell apoptosis and cytotoxicity. These findings may provide insight into the pathological processes within the pancreatic islet microvasculature induced by AGEs accumulation.

  10. Scopoletin Protects against Methylglyoxal-Induced Hyperglycemia and Insulin Resistance Mediated by Suppression of Advanced Glycation Endproducts (AGEs Generation and Anti-Glycation

    Directory of Open Access Journals (Sweden)

    Wen-Chang Chang

    2015-02-01

    Full Text Available Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the positive regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2. In this study, we investigated the ability of scopoletin (SP to protect against MG-induced hyperglycemia and insulin resistance. Recently, SP was shown to be a peroxisome proliferator-activated receptor-γ activator to elevate insulin sensitivity. We investigated the effects of oral administration of SP on the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats to understand the potential mechanism of scopoletin for diabetes protection. Our results suggested that SP activated Nrf2 by Ser40 phosphorylation, resulting in the metabolism of MG into d-lactic acid and the inhibition of AGEs generation, which reduced the accumulation of AGEs in the livers of MG-induced rats. In this manner, SP improved the results of the oral glucose tolerance test and dyslipidemia. Moreover, SP also increased the plasma translocation of glucose transporter-2 and promoted Akt phosphorylation caused by insulin treatment in MG-treated FL83B hepatocytes. In contrast, SP effectively suppressed protein tyrosine phosphatase 1B (PTP1B expression, thereby alleviating insulin resistance. These findings suggest that SP acts as an anti-glycation and anti-diabetic agent, and thus has therapeutic potential for the prevention of diabetes.

  11. Assessment of the concentrations of various advanced glycation end-products in beverages and foods that are commonly consumed in Japan.

    Directory of Open Access Journals (Sweden)

    Masayoshi Takeuchi

    Full Text Available Dietary consumption has recently been identified as a major environmental source of pro-inflammatory advanced glycation end-products (AGEs in humans. It is disputed whether dietary AGEs represent a risk to human health. Nε-(carboxymethyllysine (CML, a representative AGE compound found in food, has been suggested to make a significant contribution to circulating CML levels. However, recent studies have found that the dietary intake of AGEs is not associated with plasma CML concentrations. We have shown that the serum levels of glyceraldehyde-derived AGEs (Glycer-AGEs, but not hemoglobin A1c, glucose-derived AGEs (Glu-AGEs, or CML, could be used as biomarkers for predicting the progression of atherosclerosis and future cardiovascular events. We also detected the production/accumulation of Glycer-AGEs in normal rats administered Glu-AGE-rich beverages. Therefore, we assessed the concentrations of various AGEs in a total of 1,650 beverages and foods that are commonly consumed in Japan. The concentrations of four kinds of AGEs (Glu-AGEs, fructose-derived AGEs (Fru-AGEs, CML, and Glycer-AGEs were measured with competitive enzyme-linked immunosorbent assays involving immunoaffinity-purified specific antibodies. The results of the latter assays indicated that Glu-AGEs and Fru-AGEs (especially Glu-AGEs, but not CML or Glycer-AGEs, are present at appreciable levels in beverages and foods that are commonly consumed by Japanese. Glu-AGEs, Fru-AGEs, CML, and Glycer-AGEs exhibited concentrations of ≥85%, 2-12%, <3%, and trace amounts in the examined beverages and ≥82%, 5-15%, <3%, and trace amounts in the tested foods, respectively. The results of the present study indicate that some lactic acid bacteria beverages, carbonated drinks, sugar-sweetened fruit drinks, sports drinks, mixed fruit juices, confectionery (snacks, dried fruits, cakes, cereals, and prepared foods contain markedly higher Glu-AGE levels than other classes of beverages and foods. We

  12. COVALENT BINDING ANTIBODIES SUPPRESS ADVANCED GLYCATION: ON THE INNATE TIER OF ADAPTIVE IMMUNITY

    OpenAIRE

    Shcheglova, T.; Makker, S.; Tramontano, A

    2009-01-01

    Non-enzymatic protein glycation is a source of metabolic stress that contributes to cytotoxicity and tissue damage. Hyperglycemia has been linked to elevation of advanced glycation endproducts, which mediate much of the vascular pathology leading to diabetic complications. Enhanced glycation of immunoglobulins and their accelerated vascular clearance is proposed as a natural mechanism to intercept alternative advanced glycation endproducts, thereby mitigating microvascular disease. We reporte...

  13. The effect of fibroblast growth factors and advanced glycation end-products on the intima-media complex thickness in patients with coronary heart disease and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ekaterina Vladimirovna Ivannikova

    2014-05-01

    Full Text Available ObjectiveTo determine the levels of fibroblast transforming growth factor (TGFβ1, basic fibroblast growth factor (β-FGF, markers of nonspecific inflammatory response (interleukin-6 (IL-6, C-reactive protein (CRP, advanced glycation end-products (AGEs and their receptors (RAGEs and to study their effect on the intima-media complex (IMC thickness in patients with coronary heart disease (CHD and type 2 diabetes, depending on carbohydrate metabolism compensation.Materials and Methods37 patients with CHD underwent a general clinical examination, analysis of the carbohydrate and lipid metabolism parameters and the renal function, and also were evaluated with instrumental methods of analysis (echocardiography, coronary angiography and duplex scanning of the brachiocephalic arteries. To determine the level of the analyzed parameters, blood samples were taken from the aorta during coronary angiography and concomitantly from the cubital vein in all patients.ResultsThe presence of diabetes mellitus (DM in patients with CHD was found to be associated with a more severe atherosclerotic disease of the coronary and brachiocephalic vessels. A direct correlation between the degree of stenosis and the level of fibroblast growth factors, inflammatory factors, and advanced glycation end-products was found. A direct correlation between AGE and TGFβ1 and the lipid metabolism parameters was established. A statistically significant elevation of the studied parameters in the arterial and venous blood of patients with DM was revealed.ConclusionThese findings confirm the relationship between connective tissue disorders and lipid metabolism in the pathogenesis of atherosclerosis. A negative effect of hyperglycaemia on atherosclerotic changes of the vascular wall was demonstrated.

  14. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP and advanced glycation end-products (AGE, RAGE in patients with ischemic heart disease and type 2 diabetes mellitus

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    Ekaterina Vladimirovna Ivannikova

    2013-11-01

    Full Text Available Aims. To evaluate plasma levels of transforming growth factor beta (TGFβ1, basic fibroblast growth factor (bFGF, markers for nonspecific inflammatory process (interleukin-6 (IL-6, tumor necrosis factor alpha (TNF-α, C-reactive protein (CRP and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD.Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standard clinical examination, including laboratory assessment of glycemic parameters, lipid panel and renal function, with echocardiography, supplemented with coronary angiography. Analyses for study parameters were performed on samples obtained from aorta and, separately, from cubital vein during coronary angiography.Results. Diabetes mellitus in patients with IHD is firmly associated with TGFβ1, IL-6 and CRP elevation in both arterial and venous plasma. TGFβ1 positively correlates with lipid profile parameters. Plasma concentration of inflammatory markers and advanced glycation end-products positively correlates with the extent of coronary lesions in relation to the presence of diabetes mellitus.Conclusion. Our data suggests the interplay between connective tissue growth factors and lipid metabolism in the atherosclerotic process.

  15. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

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    Zhengyu Zhang

    2013-11-01

    Full Text Available Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes.

  16. Rosiglitazone inhibits expression of acyl-coenzyme A:cholesterol acyltransferase-1 in THP-1 macrophages induced by advanced glycation end-products

    Institute of Scientific and Technical Information of China (English)

    Yang Qihong; Xu Qiang; Zhang Hong; Si Liangyi

    2008-01-01

    Objective: To investigate the effects of rosiglitazone, a synthetic ligand of peroxisome proliferators-activated receptor gamma (PPARγ), on the expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) in phorbol myristate acetate (PMA)-pretreated THP-1 cells after the inducement of advanced glycation end products (AGEs). Methods: After THP-1 cells were cultured in the presence of 0.1 umol/L PMA for 72 h to induce phagocytic differentiation, the obtained THP-1 macrophages were treated with rosiglitazone for 4 h at different concentrations (1,5 or 10 μmol/L) and then exposed to AGEs-modified bovine serum albumin (AGEs-BSA) for 24 h at a concentration of 200 mg/L. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis were performed to detect the mRNA and protein expressions of ACAT-1 respectively. Results: Administration of AGEs-BSA (200 mg/L) into the THP-1 macrophages resulted in up-regulation of ACAT-1 at mRNA and protein levels when compared with the expressions in macrophages incubated with serum-free RPM11640. Pretreatment of rosiglitazone inhibited significantly the increased expression of ACAT-1 induced by AGEs-BSA in a concentration-dependent manner. Conclusion: PPARγ activation by rosiglitazone down-regulates ACAT-1 expression induced by AGEs in THP-1 macrophages, which might provide a new way for treating atherogenesis in diabetic patients.

  17. Vascular Effects of Advanced Glycation End-Products: Content of Immunohistochemically Detected AGEs in Radial Artery Samples as a Predictor for Arterial Calcification and Cardiovascular Risk in Asymptomatic Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Katarzyna Janda

    2015-01-01

    Full Text Available Objectives. Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters. Materials and Methods. The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed. Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH scavenging, serum C-reactive protein (hsCRP, plasminogen activator inhibitor-1 (PAI-1, and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified. Results. Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient’s age. Conclusions. The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

  18. Produtos da glicação avançada dietéticos e as complicações crônicas do diabetes Dietetics advanced glycation end-products and chronic complications of diabetes

    Directory of Open Access Journals (Sweden)

    Júnia Helena Porto Barbosa

    2009-02-01

    a conduta terapêutica, concorrendo para a melhoria da qualidade de vida dos portadores dessa enfermidade.The generation of advanced glycation end products is one of the principal mechanisms that lead to the pathologies associated with diabetes mellitus, which include cardiopathy, retinopathy, neuropathy and nephropathy. The objective of this revision is to analyse the role of the advanced glycation end products present in food as intermediaries of diabetic complications, presenting strategies to reduce their ingestion. For this purpose, research was carried out in databases of publications of the area, for the last 15 years, taking into account revision, experimental and clinical studies. Advanced glycation end products are a heterogenous group of molecules coming from non-enzymatic reactions between amino and carbonyl groups, examples being carboxymethyllisine and pentosidine found in food and in vivo. The advanced glycation end products ingested are absorbed and, along with endogenous advanced glycation end-products, promote the progression of the complications of diabetes. There is a direct correlation between advanced glycation end products consumption and blood concentration. Their restriction in food results in the suppression of serum levels of the markers of vascular disease and the intermediaries of inflammation directly involved in the development of diabetic degenerations. The current dietary orientations are concentrated on the proportion of nutrients and on energetic restriction. The risk of ingestion of advanced glycation end products formed during the processing of food should be taken in consideration. It is simply recommended that in the preparation of food, the use of low temperatures for short periods, in the presence of water, has important effects in the prevention of the complications of diabetes. The study of the mechanisms involved in the generation of advanced glycation end products and the antiglycation properties of compounds presented in

  19. Inhibition of Advanced Glycation End-Product Formation by Origanum majorana L. In Vitro and in Streptozotocin-Induced Diabetic Rats

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    Rosa Martha Perez Gutierrez

    2012-01-01

    Full Text Available The development of AGE inhibitors is considered to have therapeutic potential in patients with diabetes diseases. The aim of the present study was investigate the effect of methanolic extract of the leaves of Origanum majorana (OM used as spice in many countries on AGEs formation. In vitro studies indicated a significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal, an intermediate reactive carbonyl of AGE formation. The results demonstrate that OM have significant effects on in vitro AGE formation, and the glycation inhibitory activity was more effectively than those obtained using as standard antiglycation agent aminoguanidine. OM is a potent agent for protecting LDL against oxidation and glycation. Treatment of streptozotocin-diabetic mice with OM and glibenclamide for 28 days had beneficial effects on renal metabolic abnormalities including glucose level and AGEs formation. Diabetic mice showed increase in tail tendon collagen, glycated collagen linked fluorescence and reduction in pepsin digestion. Treatment with OM improved these parameters when compared to diabetic control and glibenclamide.

  20. Expression of advanced glycation end-products on sun-exposed and non-exposed cutaneous sites during the ageing process in humans.

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    Maria Crisan

    Full Text Available The glycation process is involved in both the intrinsic (individual, genetic and extrinsic (ultraviolet light, polution and lifestyle aging processes, and can be quantified at the epidermal or dermal level by histological, immunohistochemical (IHC, or imagistic methods. Our study is focused on a histological and immunohistological comparison of sun-protected regions versus sun-exposed regions from different age groups of skin phototype III subjects, related to the aging process. Skin samples collected from non-protected and UV protected regions of four experimental groups with different ages, were studied using histology and IHC methods for AGE-CML [N(epsilon-(carboxymethyllysine]. A semi-quantitative assessment of the CML expression in the microvascular endothelium and dermal fibroblasts was performed. The Pearson one-way ANOVA was used to compare data between the groups. In the dermis of sun-exposed skin, the number and the intensity of CML positive cells in both fibroblasts and endothelial cells (p<0.05 was higher compared to sun-protected skin, and was significantly increased in older patients. The sun-exposed areas had a more than 10% higher AGE-CML score than the protected areas. No statistically significant correlation was observed between the histological score and the IHC expression of CML. We concluded that in healthy integument, the accumulation of final glycation products increases with age and is amplified by ultraviolet exposure. The study provides new knowledge on differences of AGE-CML between age groups and protected and unprotected areas and emphasizes that endothelium and perivascular area are most affected, justifying combined topical and systemic therapies.

  1. 晚期糖基化终末产物在光老化皮肤中的表达%Expression of advanced glycation end-products in photoaging skin

    Institute of Scientific and Technical Information of China (English)

    郑瑞; 董志姗; 李灵敏; 张嘉; 郝建春; 冯艳

    2014-01-01

    Objective To detect the expression of advanced glycation end-products (AGEs) in the sun exposure and non-exposure skin,to observe the elastic protein in the same location,and to explore the relationship between non-enzymatic glycation reactions and,photo-aging skin morphological changes.Methods In the exposure and non-exposure specimens from 30 patients,elastic fibers were stained with Gomori staining,and immunohistochemistry for AGEs was performed.Results AGEs expressed clearly positive in all elastic fibers of degeneration markedly (+ + above) of exposure skin,and appeared line-like in markedly(+ + above)elastic fibers.While in all non-exposure skin,AGEs expressed negative.In the exposure skin with middle or old age,compared with non-exposure skin,AGEs expressed more and elastic fibers were hyperplasia with thickening,curling and irregular distribution.The skin parts of AGEs expressed accorded with where elastic fibers degenerated.Conclusions Ultraviolet radiation can induce denaturation of elastic fibers and non-enzymatic glycation may contribute to the mechanism of skin photo-aging.%目的 观察光暴露及非光暴露部位的皮肤组织中晚期糖基化终末产物(AGEs)的表达特点,同时对比观察弹性纤维的形态改变,探讨非酶糖基化反应(non-enzymatic glycation,NEG)与光老化皮肤形态学改变的关系.方法 对30例不同年龄的光暴露和非光暴露皮肤标本,采用醛品红法染色观察弹性纤维的变化及SP免疫组织化学检测AGEs表达.结果 光暴露部位弹力纤维变性分级++以上标本中,均有明显的AGEs表达;++以下标本有线状分布的AGEs表达.非光暴露标本中,AGEs表达均为阴性.同一年龄,光暴露和非光暴露标本中,光暴露部位的AGEs的表达明显高于非光暴露部位,同时出现弹性纤维明显增多、增粗,出现扭曲、不规则分布.AGEs的表达同弹性纤维发生变性部位基本相符.结论 NEG反应在皮肤光老化的发生机制中可能有一定的作用.

  2. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  3. Barley malt increases hindgut and portal butyric acid, modulates gene expression of gut tight junction proteins and Toll-like receptors in rats fed high-fat diets, but high advanced glycation end-products partially attenuate the effects.

    Science.gov (United States)

    Zhong, Yadong; Teixeira, Cristina; Marungruang, Nittaya; Sae-Lim, Watina; Tareke, Eden; Andersson, Roger; Fåk, Frida; Nyman, Margareta

    2015-09-01

    Barley malt, a product of controlled germination, has been shown to produce high levels of butyric acid in the cecum and portal serum of rats and may therefore have anti-inflammatory effects. The aim of the study was to investigate how four barley malts, caramelized and colored malts, 50-malt and 350-malt, differing in functional characteristics concerning beta-glucan content and color, affect short-chain fatty acids (SCFA), barrier function and inflammation in the hindgut of rats fed high-fat diets. Male Wistar rats were given malt-supplemented high-fat diets for four weeks. Low and high-fat diets containing microcrystalline cellulose were incorporated as controls. All diets contained 70 g kg(-1) dietary fiber. The malt-fed groups were found to have had induced higher amounts of butyric and propionic acids in the hindgut and portal serum compared with controls, while cecal succinic acid only increased to a small extent. Fat increased the mRNA expression of tight junction proteins and Toll-like receptors (TLR) in the small intestine and distal colon of the rats, as well as the concentration of some amino acids in the portal plasma, but malt seemed to counteract these adverse effects to some extent. However, the high content of advanced glycation end-products (AGE) in caramelized malt tended to prohibit the positive effects on occludin in the small intestine and plasma amino acids seen with the other malt products. In conclusion, malting seems to be an interesting process for producing foods with positive health effects, but part of these effects may be destroyed if the malt contains a high content of AGE. PMID:26227569

  4. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence.

    Science.gov (United States)

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian

    2011-10-01

    Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors

  5. 糖基化终产物受体在大鼠牙周膜成纤维细胞中的表达%Expression of receptor for advanced glycation end-product in rat periodontal ligament fibroblasts

    Institute of Scientific and Technical Information of China (English)

    邓天政; 吕晶; 冯岩; 李冬霞; 刘冰; 逄键梁; 柯杰

    2012-01-01

    Objective To detect expression of receptor for advanced glycation end products (RAGE) produced by human periodontal ligament fibroblasts ( PDL) cultured in vitro. Methods To collect rat periodontal ligament firbroblast induced by 50, 100, 200 mg/L advanced glycation end products-bovine serum albumin ( AGE-BSA) 200 mg/L BSA and blank control in DMEM in vitro, which were group A, B, C, D, E respectively. Detect mRNA of RAGE using RT-PCR and protein expression using immunohistochemistry. Results Immunohistochemistry showed the protein expression ofRAGE in group A, B, C, and the expression level elevated with the increase of AGE-BSA concentration. Group D and E did not express RAGE protein. RT-PCR proved the gene of RAGE expresses in group A, B, C. Group D expressed a little, group E did not express. Conclusion RAGE can be produced by PDL cultured in vitro induced by AGE-BSA.%目的 研究体外培养大鼠牙周膜成纤维细胞在糖基化终产物诱导下糖基化终产物受体( receptor for advanced glycation end-product,RAGE)的表达情况.方法 收集第三代体外培养的大鼠牙周膜成纤维细胞,在含有终浓度为50、100、200 mg/L的糖基化牛血清白蛋白、200 ms/L的牛血清白蛋白以及不含上述蛋白成分培养基内孵育48h,分别设为A组、B组、C组、D组、E组.免疫组织化学法、反转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)检测细胞内RAGE蛋白及mRNA表达.结果 免疫组织化学结果显示A、B、C组中牙周膜成纤维细胞内RAGE蛋白表达均为阳性,且随浓度增高,表达强度略有增强,而D及E组无表达;RT-PCR检测发现A、B、C组RAGE mRNA均表达且表达强度随浓度增高而增强,D组有少量表达,E组不表达.结论 体外培养的牙周膜成纤维细胞在糖基化终产物诱导下能够表达RAGE.

  6. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence.

    Science.gov (United States)

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian

    2011-10-01

    Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors

  7. The pecking order of skin Advanced Glycation Endproducts (AGEs) as long-term markers of glycemic damage and risk factors for micro- and subclinical macrovascular disease progression in Type 1 diabetes.

    Science.gov (United States)

    Monnier, Vincent M; Genuth, Saul; Sell, David R

    2016-08-01

    To date more than 20 glycation products were identified, of which ~15 in the insoluble human skin collagen fraction. The goal of this review is to streamline 30 years of research and ask a set of important questions: in Type 1 diabetes which glycation products correlate best with 1) past mean glycemia 2) reversibility with improved glycemic control, 2) cross-sectional severity of retinopathy, nephropathy and neuropathy and 3) the future long-term risk of progression of micro- and subclinical macrovascular disease. The trio of glycemia related glycation markers furosine (FUR)/fructose-lysine (FL), glucosepane and methylglyoxal hydroimidazolone (MG-H1) emerges as extraordinarily strong predictors of existing and future microvascular disease progression risk despite adjustment for both past and prospective A1c levels. X(2) values are up to 25.1, p values generally less than 0.0001, and significance remains after adjustment for various factors such as A1c, former treatment group, log albumin excretion rate, abnormal autonomic nerve function and LDL levels at baseline. In contrast, subclinical cardiovascular progression is more weakly correlated with AGEs/glycemia with X(2) values collagen solubility), adjusted FUR and Collagen Fluorescence (CLF) are the strongest markers for future coronary artery calcium deposition, while cardiac hypertrophy is associated with LW-1 and CLF adjusted for A1c. We conclude that a robust clinical skin biopsy AGE risk panel for microvascular disease should include at least FUR/FL, glucosepane and MG-H1, while a macrovascular disease risk panel should include at least FL/FUR, MG-H1, LW-1 and CLF. PMID:27342131

  8. Simple non-invasive assessment of advanced glycation endproduct accumulation

    NARCIS (Netherlands)

    Meerwaldt, R; Graaff, R; Links, TP; Jager, JJ; Alderson, NL; Thorpe, [No Value; Baynes, JW; Gans, ROB; Smit, AJ

    2004-01-01

    Aims/hypothesis. The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a

  9. 高糖及糖基化终末产物对人脂肪干细胞成骨分化能力的影响%Effects of high glucose and advanced glycation end-products on osteogenic differentiation of human adipose-derived stromal cells in vitro

    Institute of Scientific and Technical Information of China (English)

    李冬松; 李叔强; 蔡波; 王苹; 冯卫; 刘建国

    2011-01-01

    BACKGROUND: Bone metabolism disorder happens in diabetic environment, bone defects in which are difficult to repair. Study addressing osteogenic property of adipose-derived stroma cells (ADSCs) in diabetic environment provides theoretical basis for its application in certain environment.OBJECTIVE: To explore the effects of high glucose (HG) and advanced glycation end-products (AGEs) on osteogenic capacity of human ADSCs. METHODS: 100 mg/L AGEs and 27.5 mmol/L HG were used to simulate in vitro diabetic environment and intervened ADSCs osteogenic differentiation. The cells were divided into 4 groups, with 6 samples in each group. The expression of type Ⅰ collagen was examined by fluorescent immunofluorescence at 21 days after osteogenic induction. The number of calcification nodes was counted under contrast phase microscopy at 14, 21 and 28 days. RESULTS AND CONCLUSION: Fluorescent quantitation scan showed that the type Ⅰ collagen amount of the AGEs+HG treated group was 2.76 times lower than that of the control group. AGEs+HG reduced the number of ADSCs calcification nodes compared with the control, HG, and AGEs groups, the differences were statistical significant (P < 0.01). AGEs and HG exposure inhibit the cognate osteogenic differentiation of ADSCs, which suggest that AGEs and HG are unfavorable factors that reduce ADSCs osteogenic ability.%背景:因糖尿病条件下骨质代谢存在紊乱,对这类骨缺损的修复具有挑战性,研究糖尿病环境下脂肪干细胞的成骨特性将为其在特定环境下的应用提供理论基础.目的:观察高糖、糖基化终末产物对人脂肪干细胞成骨分化能力的影响.方法:选取27.5 mmol/L高糖、100 mg/L糖基化终末产物体外模拟糖尿病环境,干预人脂肪干细胞成骨分化;实验分为4组,每组设立6个样本.通过荧光染色检测脂肪干细胞诱导成骨21 d时的Ⅰ型胶原表达量,矿化结节染色观测各组中等量脂肪干细胞在14,21,28 d时矿化结节

  10. 黄连多糖对AGEs诱导内皮细胞增殖及其受体表达的作用研究%Effects of Polysaccharides from Coptis Chinensis on HUVECs Proliferation Induced by Advanced Glycation Endproducts and Expression of Its Receptor

    Institute of Scientific and Technical Information of China (English)

    尹登科; 杨晔; 陈松; 李云; 高向东

    2012-01-01

    To study the effects of Coptis Chinensis polysaccharide (CCP) on HUVECs proliferation induced by advanced glycation endproducts(AGEs) and the expression of the receptor for AGEs(RAGE) ,the total CCP was prepared by water extraction, depro-teinized by method of sevag,and alcohol precipitation. HUVECs with 80% confluent were divided into six groups as control (without treatment) ,BSA group ( 200 μg /mL) , AGEs group(200 μg/mL, protein concentration) , AGEs + CCP(25 μg/mL) , AGEs + CCP (50 μg/mL) and AGEs + CCP ( 100 μg/mL) , The proliferation of HUVECs was determined by the method of MTT, Real Time Quantitative Fluorescence RCR was used to analyze the expression of RAGE rnRNA and Western Blot was used to detect the expression of RAGE, The proliferation of HUVECs was increased after treatment with AGEs for 48 h, CCP significantly inhibited the pro-proliferation of HUVECs induced by AGEs in dose-dependent manner. The results of PCR and Western Blot also demonstrated that CCP could decrease the expression of RAGE mRNA and protein. CCP inhibited the activation of HUVECs induced by AGEs through inhibiting the expression of RAGE.%考察黄连多糖对高级糖基化终产物(AGEs)诱导人脐静脉内皮细胞(HUVECs)增殖和AGEs受体(RAGE)表达的作用.采用水提,Sevag法去蛋白,醇沉法获得黄连多糖(CCP);80%汇聚的HUVECs分成6组,分别为空白对照组、BSA对照组(蛋白浓度200μg/mL)、AGEs组(蛋白浓度200μg/mL)、AGEs+ CCP(25μg/mL)、AGEs+ CCP(50 μg/mL)和AGEs+ CCP(100μg/mL),采用MTT法检测黄连多糖对AGEs诱导HUVECs增殖的影响;实时荧光定量PCR检测RAGE mRNA表达;Westem Blot分析RAGE蛋白表达情况.HUVECs经AGEs诱导48h后,其增殖率显著增殖.黄连多糖可以剂量依赖性的抑制AGEs诱导HUVECs早期增殖作用,定量PCR和Western Blot结果表明CCP可以在mRNA和蛋白水平抑制RAGE表达.黄连多糖可通过抑制RAGE表达,降低AGEs对内皮细胞的激活作用.

  11. Advanced glycation end product ligands for the receptor for advanced glycation end products: Biochemical characterization and formation kinetics

    NARCIS (Netherlands)

    Valencia, J.V.; Weldon, S.C.; Quinn, D.; Kiers, G.H.; Groot, J. de; TeKoppele, J.M.; Hughes, T.E.

    2004-01-01

    Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown.

  12. The Clinical Significances of Soluble Receptor for Advanced Glycation Endproducts in Bronchoscopy Alveolus Lavage Fluid among Patients with COPD%COPD纤维支气管镜肺泡灌洗液中可溶性晚期糖基化终末产物受体水平的临床意义

    Institute of Scientific and Technical Information of China (English)

    杨兴官; 雷超; 胡占升

    2014-01-01

    Objective To discuss the clinical significances of soluble receptor for advanced glycation end-products ( sRAGE)in bronchoscopy alveolus lavage fluid( BALF)in patients with COPD. Methods A total of 40 patients with COPD who were admitted to the department of intensive care unit of the First Hospital Affiliated to Liaoning Medical University from Oc-tober 2012 to May 2013,were selected as the COPD group,meanwhile 40 patients with non-COPD were selected as the non-COPD group,and these COPD patients were divided into mild group(12 cases),moderate group(10 cases),severe group (10 cases),very severe group(8 cases). The sRAGE concentrations in BALF were detected by enzyme-linked immunosor-bent assay(ELISA). Results The concentration of sRAGE in BALF of patients in the COPD group(191 ±71)ng/L was sig-nificantly higher than that in the non-COPD group(55 ±56)ng/L(t=9. 44,P<0. 001). The concentration of sRAGE in BALF of COPD patients in the mild group,moderate group,severe group and very severe group was(111 ± 44) ng/L,(184 ±45)ng/L,(226 ±34)ng/L,and(273 ±30)ng/L,respectively,there were significant differences in concentration of sRAGE among these groups(F=30. 48,P<0. 001),and the concentration of sRAGE in very severe COPD group was signifi-cantly higher than that in severe COPD group,the concentration of sRAGE in severe COPD group was significantly higher than that in moderate group,the concentration of sRAGE in moderate group was significantly higher than that in mild group( P <0. 05 ) . Linear correlation analysis results showed that the concentration of sRAGE in BALF of COPD patients were negatively cor-related with FEV1%(r= -0. 738,P <0. 05). Conclusion The concentration of sRAGE in BALF of COPD patients was higher than that of non-COPD patients;The concentration of sRAGE in BALF is related to severity of COPD,it could be used as an index of the prognosis evaluation of COPD.%目的:探讨纤维支气管镜肺泡灌洗液中可溶性晚期

  13. Expression of Receptor for Advanced Glycation Endproduct on Peripheral Blood Mononuclear Cells in Patients with Coronary Heart Disease%冠心病患者外周血单核细胞表面晚期糖基化终末产物受体水平的表达

    Institute of Scientific and Technical Information of China (English)

    周鹤; 牛楠; 曲鹏; 解丽颖; 杨丽

    2013-01-01

    目的探讨外周血单核细胞表面晚期糖基化终末产物受体(RAGE)的表达水平与冠心病患者临床表现及冠状动脉病变严重程度的关系,并评估其对冠心病患者风险的预测价值.方法 选择因胸痛住院并行冠状动脉造影的患者80例,据其不同临床表现、冠状动脉病变的Gensini积分、病变血管支数进行相应分组,采用流式细胞学方法测定外周血单核细胞表面RAGE水平.结果 急性心肌梗死组、不稳定型心绞痛组外周血单核细胞表面RAGE表达水平均高于稳定型心绞痛组和对照组(P<0.01).RAGE水平与高敏C反应蛋白水平呈正相关(r=0.476,P=0.01);多支病变组和两支病变组外周血单核细胞表面RAGE表达水平高于单支病变组(P<0.05);多支病变组RAGE水平高于两支病变组(P<0.05);根据冠状动脉造影Gensini评分分为三组,三组间外周血单核细胞表面RAGE水平逐渐升高,且各组间差异均具有统计学差异.外周血单核细胞表面RAGE水平与冠状动脉造影评分之间呈正相关(r=0.376,P=0.007);采用Logistic回归法分析高水平的外周血单核细胞表面RAGE水平是冠心痛患者发生急性冠状动脉综合征的独立危险因素(OR=1.180,P=0.02).结论 冠心病患者外周血单核细胞表面RAGE表达水平明显增加,且随着临床表现严重程度的增加呈逐渐升高趋势,对冠心病患者的临床表现有预测价值.外周血单核细胞RAGE水平与冠状动脉病变狭窄程度相关,对冠状动脉病变严重程度有一定的预测价值.高水平外周血单核细胞RAGE的表达是冠心痛患者临床表现严重程度的独立危险因素.%Aim To analyze the relationship between the level of receptor for advanced glycation endproducts (RAGE) on peripheral blood mononuclear cells (PBMC) and the clinical manifestations of coronary heart disease and the severity of angiographic lesion. Further investigation should be made to discuss

  14. Inhibition of Nonenzymatic Protein Glycation by Pomegranate and Other Fruit Juices

    OpenAIRE

    Dorsey, Pamela Garner; Greenspan, Phillip

    2014-01-01

    The nonenzymatic glycation of proteins and the formation of advanced glycation endproducts in diabetes leads to the crosslinking of proteins and disease complications. Our study sought to demonstrate the effect of commonly consumed juices (pomegranate, cranberry, black cherry, pineapple, apple, and Concord grape) on the fructose-mediated glycation of albumin. Albumin glycation decreased by 98% in the presence of 10 μL of pomegranate juice/mL; other juices inhibited glycation by only 20%. Pome...

  15. Dietary Advanced Glycation End Products and Aging

    Directory of Open Access Journals (Sweden)

    Karen Chapman-Novakofski

    2010-12-01

    Full Text Available Advanced glycation end products (AGEs are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food and endogenously (in humans with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.

  16. Efectos de los productos de glicación avanzada (AGEs y alendronato sobre el desarrollo osteoclástico: posibles mecanismos de acción Effect of Advanced Glycation Endproducts and Alendronate on osteoclastic development: possible mechanisms of action

    Directory of Open Access Journals (Sweden)

    María Virginia Gangoiti

    2012-03-01

    alendronato (10-5M no modificaron la expresión del RAGE en los cocultivos incubados con BSA (95 % respecto de BSA. Por otro lado, bajas dosis de alendronato en presencia de AGEs no alteraron la "up-regulation" del RAGE inducida por los AGEs (145 % respecto de BSA. Sin embargo, cuando los Oc se incubaron con AGEs y Ale 10-5M, esta dosis del bifosfonato bloqueá el efecto estimulante de los AGEs sobre la expresión de RAGE (105 % respecto de BSA. La incubación con 100 µg/ml AGE produjo una inhibición (50 % respecto de BSA, en la expresión del RANKL en los osteoblastos. El alendronato (10-8M-10-5M indujo también una inhibición del RANKL en forma dosis dependiente (65-47 % respecto de BSA. Por otro lado en presencia de AGEs, el alendronato (10-8M-10-5M no modificá la inhibición de la expresión del RANKL inducida por los AGEs (59-45 % del BSA. Conclusiones: Los AGEs y el alendronato inhiben el número y diferenciación de Oc en cultivo, con un efecto aditivo entre ambos a altas concentraciones de alendronato. También reducen la expresión de RANKL en osteoblastos, lo cual podría explicar parcialmente sus efectos sobre el reclutamiento y la maduración de Oc. Los AGEs y bajas dosis de alendronato aumentan la expresión de RAGE en Oc.Introduction: Patients with Diabetes mellitus frequently show osteopenia and/or osteoporosis, as well as an increase in low-trauma fracture risk. This has been postulated to be caused partially by the accumulation of advanced glycation endproducts (AGEs in bone extracellular matrix. AGEs could affect the homeostasis of bone cells, such as osteoblasts, osteocytes and osteoclasts. Osteoclasts (Oc are multi-nucleated cells specialized in resorbing bone. Bisphosphonates (BP are drugs widely used for treatment of bone diseases, and their principal mechanism of action is to inhibit the resorptive action of Oc. However, the use of BP for the treatment of patients with Diabetes-related bone disease is still controversial. Objective: To study the

  17. Targeting advanced glycation with pharmaceutical agents: where are we now?

    Science.gov (United States)

    Borg, Danielle J; Forbes, Josephine M

    2016-08-01

    Advanced glycation end products (AGEs) are the final products of the Maillard reaction, a complex process that has been studied by food chemists for a century. Over the past 30 years, the biological significance of advanced glycation has also been discovered. There is mounting evidence that advanced glycation plays a homeostatic role within the body and that food-related Maillard products, intermediates such as reactive α-dicarbonyl compounds and AGEs, may influence this process. It remains to be understood, at what point AGEs and their intermediates become pathogenic and contribute to the pathogenesis of chronic diseases that inflict current society. Diabetes and its complications have been a major focus of AGE biology due to the abundance of excess sugar and α-dicarbonyls in this family of diseases. While further temporal information is required, a number of pharmacological agents that inhibit components of the advanced glycation pathway have already showed promising results in preclinical models. These therapies appear to have a wide range of mechanistic actions to reduce AGE load. Some of these agents including Alagebrium, have translated successfully to clinical trials, while others such as aminoguanidine, have had undesirable side-effect profiles. This review will discuss different pharmacological agents that have been used to reduce AGE burden in preclinical models of disease with a focus on diabetes and its complications, compare outcomes of those therapies that have reached clinical trials, and provide further rationale for the use of inhibitors of the glycation pathway in chronic diseases. PMID:27392438

  18. Effects of advanced glycation end-products on the expression of parathyroid hormone related peptide and vascular calcification on vascular smooth muscle cells%糖基化终产物对人血管平滑肌细胞表达及分泌甲状旁腺激素相关肽和血管钙化的影响

    Institute of Scientific and Technical Information of China (English)

    张琴; 刘乃丰

    2014-01-01

    Objective:To investigate the effects of advanced glycation end-products(AGEs) on expression and secretion of parathyroid hormone related peptide(PTHrP)in vitro cultured human vascular smooth muscle cells (HVSMCs), and explore the related mechanism of PTHrP influencing vascular smooth muscle cells calcification . Methods:HVSMCs were treated with AGE-BSA of indicated concentration or non-glycated BSA for same periods . The calcium contents and activity of alkaline phosphatase of cells were analyzed by microplate reader ;PTHrP levels in the supernatant were detected by the enzyme-linked immunosorbent method .Real-time fluorescent quantitative reverse transcription polymerase chain reaction ( RT-PCR) was performed to detect the expressive of PTHrP , core- binding factor α1(cbfα1) in human and bone morphogenetic protein-2(BMP-2) in vascular smooth muscle cells . Results:AGE-BSA increased calcium deposition and activity of alkaline phosphatase in HVSMCs in dose-independent manners( P<0.05) , but reduced the secretion of PTHrP.Futhermore, the elevated AGE-BSA treatment on HVSMCs significantly enhanced the expression of cbfα1, BMP-2 and PTHrP, compared with the controls( P <0.05 ) .Conclusion: The expression and secretion of PTHrP on human vascular smooth muscle cells can be effected by AGEs , and PTHrP may induce deposition of calcium on vascular smooth muscle cells, thereby contributing to the vascular calcification .However, the related mechanism will be further explored .%目的:观察糖基化终末产物(AGEs)对人血管平滑肌细胞表达及分泌甲状旁腺激素相关肽(PTHrP)功能的影响,探讨PTHrP影响血管平滑肌细胞钙化发生的相关机制。方法:不同浓度的AGE-BSA分别与人血管平滑肌细胞孵育相同时间后,检测各组细胞钙含量及碱性磷酸酶( ALP)活性判断钙化程度;酶联免疫吸附法检测各组细胞PTHrP的分泌量;实时荧光定量逆转录聚合酶链反应检

  19. Advanced glycation end products in renal failure: an overview.

    Science.gov (United States)

    Noordzij, M J; Lefrandt, J D; Smit, A J

    2008-12-01

    The article aims to present an overview of the existing knowledge on advanced glycation end products (AGE). They are moieties that bind to proteins, but also lipids and nuclear acids. AGE are formed during glycation and oxidative stress. Accumulation of AGE occurs especially in diabetes and chronic renal failure and plays a major pathogenetic role. The deleterious effects of AGE result from cross-linking of proteins and activation of the receptor for advanced glycation end products. AGE accumulation can be noninvasively assessed by the skin autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac mortality and the occurrence of macro- and microvascular complications. In patients on haemodialysis, skin autofluorescence is highly elevated and predicts mortality. After renal transplantation AGE accumulation is lower than during haemodialysis, but still remains elevated and is a strong risk factor for chronic renal transplant dysfunction. Some of the potential methods to intervene with AGE accumulation are discussed in this article.

  20. Advanced glycation end products in renal failure: an overview.

    Science.gov (United States)

    Noordzij, M J; Lefrandt, J D; Smit, A J

    2008-12-01

    The article aims to present an overview of the existing knowledge on advanced glycation end products (AGE). They are moieties that bind to proteins, but also lipids and nuclear acids. AGE are formed during glycation and oxidative stress. Accumulation of AGE occurs especially in diabetes and chronic renal failure and plays a major pathogenetic role. The deleterious effects of AGE result from cross-linking of proteins and activation of the receptor for advanced glycation end products. AGE accumulation can be noninvasively assessed by the skin autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac mortality and the occurrence of macro- and microvascular complications. In patients on haemodialysis, skin autofluorescence is highly elevated and predicts mortality. After renal transplantation AGE accumulation is lower than during haemodialysis, but still remains elevated and is a strong risk factor for chronic renal transplant dysfunction. Some of the potential methods to intervene with AGE accumulation are discussed in this article. PMID:19090900

  1. 血清可溶性晚期糖基化终产物受体水平与系统性红斑狼疮疾病活动度的相关性%Association between Serum Levels of Soluble Receptor for Advanced Glycation End-products and Disease Activity of Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    菅夏楠; 郑朝晖; 于若寒; 刘升云; 刘章锁

    2015-01-01

    Objective The aim of our study was to investigate the value of serum soluble receptor for advanced glycation (sRAGE)levels in the estimation of disease activity of systemic lupus erythematosus (SLE). Methods 104 patients who suffered from SLE and who had been treated in our hospital from June 2013 to June 2014 were included into our study.Clinical and epidemiological data were collected.Results The concentration of sRAGE in the SLE group,the non-active SLE group,active SLE group,and the control group were (1 060.16 ±762.59),(912.06 ±759.98),(1 232.96 ±736.16),and(1 300.42 ±466.01) pg/ml respectively,so the difference was statistically significant (Z = -2.891,P =0.004 ).The difference was statistically significant among the non-active SLE group,active SLE group,and the control group (χ2 =17.999,P =0.000).There was higher serum sRAGE levels in patients whose SLE disease activity index(SLEDAI)≥10 (Z =-3.052,P =0.002)and whose titer of anti-dsDNA antibody≥100 (Z =-2.276,P =0.023),and there was positive correlation between serum sRAGE levels and SLEDAI≥10(r =0.373,P =0.000),the difference was statistically significant.Conclusion We can evaluate disease activity of SLE by detecting the serum sRAGE levels,which may provide information to guide the treatment.%目的:探讨可溶性晚期糖基化终产物受体(soluble receptor for advanced glycation end-products,sRAGE)在系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病活动度评价中的价值。方法收集2013年6月至2014年6月郑州大学第一附属医院 SLE 患者的临床及流行病学资料,观察血清 sRAGE 浓度与 SLE 疾病活动度的相关性。结果 SLE 组、非活动SLE 组、活动 SLE 组和健康对照组 sRAGE 浓度分别为(1060.16±762.59)、(912.06±759.98)、(1232.96±736.16)、(1300.42±466.01)pg/ml;SLE 组与健康对照组 sRAGE 浓度差异有统计学意义(Z =-2.891,P =0.004),非活动 SLE

  2. Immunohistochemical localisation of advanced glycation end products in pulmonary fibrosis.

    OpenAIRE

    Matsuse, T.; Ohga, E.; Teramoto, S.; Fukayama, M; Nagai, R.; Horiuchi, S; Ouchi, Y.

    1998-01-01

    AIM: To investigate the presence and distribution of advanced glycation end products (AGE) in pulmonary fibrosis. METHODS: Lung tissue samples obtained from seven necropsy cases with idiopathic pulmonary fibrosis and seven with normal pulmonary parenchyma were examined immunohistochemically with a monoclonal antibody specific for AGE: 6D12. We also tested three cases with diffuse alveolar damage. RESULTS: All the specimens from cases with pulmonary fibrosis and diffuse alveolar damage showed ...

  3. Vascular Effects of Dietary Advanced Glycation End Products

    OpenAIRE

    Alin Stirban; Diethelm Tschöpe

    2015-01-01

    Evidence has accumulated lately demonstrating that advanced glycation end products (AGEs) play an important role in the development of diabetic and cardiovascular complications as well as the development of other chronic diseases. AGEs originating from diet have a significant contribution to the AGEs body pool and therefore dietary interventions aiming at reducing AGEs load are believed to exert health promoting effects. This review summarizes the evidence from clinical studies regarding effe...

  4. Optoacoustic detection of tissue glycation.

    Science.gov (United States)

    Ghazaryan, Ara; Omar, Murad; Tserevelakis, George J; Ntziachristos, Vasilis

    2015-09-01

    Oxidative-based diseases including diabetes, chronic renal failure, cardiovascular diseases and neurological disorders are accompanied by accumulation of advanced glycation endproducts (AGE). Therefore, AGE-associated changes in tissue optical properties could yield a viable pathological indicator for disease diagnostics and monitoring. We investigated whether skin glycation could be detected based on absorption changes associated with AGE accumulation using spectral optoacoustic measurements and interrogated the optimal spectral band for skin glycation determination. Glycated and non-glycated skin was optoacoustically measured at multiple wavelengths in the visible region. The detected signals were spectrally processed and compared to measurements of skin auto-fluorescence and to second harmonic generation multiphoton microscopy images. Optoacoustic measurements are shown to be capable of detecting skin glycolysis based on AGE detection. A linear dependence was observed between optoacoustic intensity and the progression of skin glycation. The findings where corroborated by autofluorescence observations. Detection sensitivity is enhanced by observing normalised tissue spectra. This result points to a ratiometric method for skin glycation detection, specifically at 540 nm and 620 nm. We demonstrate that optoacoustic spectroscopy could be employed to detect AGE accumulation, and possibly can be employed as a non-invasive quick method for monitoring tissue glycation. PMID:26417487

  5. The inhibition of advanced glycation end-products-induced retinal vascular permeability by silver nanoparticles.

    Science.gov (United States)

    Sheikpranbabu, Sardarpasha; Kalishwaralal, Kalimuthu; Lee, Kyung-Jin; Vaidyanathan, Ramanathan; Eom, Soo Hyun; Gurunathan, Sangiliyandi

    2010-03-01

    The increased permeability of the blood-retinal barrier is known to occur in patients with diabetes, and this defect contributes to retinal edema. This study aimed to determine the effects of silver nanoparticles (Ag-NPs) on advanced glycation end-products (AGEs)-induced endothelial cell permeability. Cultured porcine retinal endothelial cells (PRECs) were exposed to AGE-modified bovine serum albumin (AGE-BSA) and the endothelial cell permeability was detected by measuring the flux of RITC-dextran across the PREC monolayers. We found that AGE-BSA increased the dextran flux across a PREC monolayer and Ag-NPs blocked the solute flux induced by AGE-BSA. In order to understand the underlying signaling mechanism of Ag-NPs on the inhibitory effect of AGE-BSA-induced permeability, we demonstrated that Ag-NPs could inhibit the AGE-BSA-induced permeability via Src kinase pathway. AGE-BSA also increased the PREC permeability by stimulating the expression of intracellular adhesion molecule-1 (ICAM-1) and decreased the expression of occludin and ZO-1. Further, Ag-NPs inhibited the AGE-BSA-induced permeability by increased expression of tight junction proteins occludin and ZO-1, co-incident with an increase in barrier properties of endothelial monolayer. Together, our results indicate that Ag-NPs could possibly act as potent anti-permeability molecule by targeting the Src signaling pathway and tight junction proteins and it offers potential targets to inhibit the ocular related diseases. PMID:19963272

  6. Mass spectrometric determination of early and advanced glycation in biology.

    Science.gov (United States)

    Rabbani, Naila; Ashour, Amal; Thornalley, Paul J

    2016-08-01

    Protein glycation in biological systems occurs predominantly on lysine, arginine and N-terminal residues of proteins. Major quantitative glycation adducts are found at mean extents of modification of 1-5 mol percent of proteins. These are glucose-derived fructosamine on lysine and N-terminal residues of proteins, methylglyoxal-derived hydroimidazolone on arginine residues and N(ε)-carboxymethyl-lysine residues mainly formed by the oxidative degradation of fructosamine. Total glycation adducts of different types are quantified by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS) in multiple reaction monitoring mode. Metabolism of glycated proteins is followed by LC-MS/MS of glycation free adducts as minor components of the amino acid metabolome. Glycated proteins and sites of modification within them - amino acid residues modified by the glycating agent moiety - are identified and quantified by label-free and stable isotope labelling with amino acids in cell culture (SILAC) high resolution mass spectrometry. Sites of glycation by glucose and methylglyoxal in selected proteins are listed. Key issues in applying proteomics techniques to analysis of glycated proteins are: (i) avoiding compromise of analysis by formation, loss and relocation of glycation adducts in pre-analytic processing; (ii) specificity of immunoaffinity enrichment procedures, (iii) maximizing protein sequence coverage in mass spectrometric analysis for detection of glycation sites, and (iv) development of bioinformatics tools for prediction of protein glycation sites. Protein glycation studies have important applications in biology, ageing and translational medicine - particularly on studies of obesity, diabetes, cardiovascular disease, renal failure, neurological disorders and cancer. Mass spectrometric analysis of glycated proteins has yet to find widespread use clinically. Future use in health screening, disease diagnosis and therapeutic monitoring, and

  7. Skin Autofluorescence as Marker of Tissue Advanced Glycation End-Products Accumulation in Formerly Preeclamptic Women

    NARCIS (Netherlands)

    Coffeng, S.M.; Blaauw, Judith; Souwer, E.T.; Rakhorst, G.; Smit, A.J.; Graaff, R.; van Doormaal, J.J.; Aarnoudse, J.G.; Faas, M.M.; van Pampus, Maria

    2011-01-01

    Condensation. In women with a history of preeclampsia skin autofluorescence as marker of tissue AGEs accumulation is increased, supporting a common causal metabolic or vascular link between preeclampsia and cardiovascular diseases. Objective. To investigate whether skin autofluorescence (AF), as mar

  8. Advanced glycation end-products and skin autofluorescence in end-stage renal disease : a review

    NARCIS (Netherlands)

    Arsov, Stefan; Graaff, Reindert; van Oeveren, Wim; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Smit, Andries J.

    2014-01-01

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are

  9. The association between glyceraldehyde-derived advanced glycation end-products and colorectal cancer risk

    NARCIS (Netherlands)

    Kong, So Yeon; Takeuchi, Masayoshi; Hyogo, Hideyuki; McKeown-Eyssen, Gail; Yamagishi, Sho Ichi; Chayama, Kazuaki; O'Brien, Peter J.; Ferrari, Pietro; Overvad, Kim; Olsen, Anja; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Bastide, Nadia; Carbonnel, Franck; Kühn, Tilman; Kaaks, Rudolf; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Vasilopoulou, Effie; Masala, Giovanna; Pala, Valeria; De Magistris, Maria Santucci; Tumino, Rosario; Naccarati, Alessio; Bueno-De-Mesquita, H. B.; Peeters, Petra H.; Weiderpass, Elisabete; Quiŕos, J. Ramón; Jakszyn, Paula; ͆anchez, María Jos̈e; Dorronsoro, Miren; Gavrila, Diana; Ardanaz, Eva; Rutegård, Martin; Nyström, Hanna; Wareham, Nicholas J.; Khaw, Kay Tee; Bradbury, Kathryn E.; Romieu, Isabelle; Freisling, Heinz; Stavropoulou, Faidra; Gunter, Marc J.; Cross, Amanda J.; Riboli, Elio; Jenab, Mazda; Bruce, W. Robert

    2015-01-01

    Background: A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls

  10. Reduction of serum advanced glycation end-products with a low calorie Mediterranean diet.

    Science.gov (United States)

    Rodríguez, Juan Manuel; Leiva Balich, Laura; Concha, M J; Mizón, C; Bunout Barnett, Daniel; Barrera Acevedo, Gladys; Hirsch Birn, Sandra; Jiménez Jaime, Teresa; Henríquez, Sandra; Uribarri, Jaime; de la Maza Cave, María Pía

    2015-06-01

    La ingesta dietaria de productos finales de glicación avanzada (AGEs) aumenta los niveles séricos y tisulares de estas sustancias, lo que contribuye a un estado de mayor estrés oxidativo e inflamación. Una intervención dietaria con bajo contenido de AGEs ha demostrado reducir el contenido de AGEs en el cuerpo. La dieta mediterránea (DM) se considera teóricamente baja en AGEs, pero los efectos específicos de este tipo de intervención en los niveles séricos de AGEs no ha sido probado. Metodología: cuarenta y siete mujeres premenopáusicas con sobrepeso u obesidad se sometieron a tres meses de restricción calórica (20 kcal por kg de peso corporal inicial) con una dieta de tipo mediterráneo que excluía la ingesta de vino. La adherencia a la DM se evaluó al comienzo y al final del tratamiento utilizando una encuesta on-line, con puntuaciones de 0 a 14 (mínima a máxima adherencia a la DM). La composición corporal, la resistencia a la insulina, los niveles séricos de lipoproteínas y carboximetil-lisina (CML) se midieron en ambos períodos. El CML sérico se evaluó mediante ELISA (ensayo inmunoenzimático). La adherencia a la restricción calórica se evaluó de acuerdo con la pérdida de peso ( 5% del peso inicial). Resultados: la media de peso corporal, grasa corporal, circunferencia de la cintura, colesterol total, triglicéridos y CML sérica disminuyeron significativamente, junto con un aumento en el puntaje de adherencia a la DM, aunque ninguno de los pacientes alcanzó la máxima puntuación. Hubo cambios significativos en los niveles de CML y de resistencia a la insulina en 17 mujeres clasificadas como adherentes a la restricción calórica, pero no en las 27 participantes que fueron consideradas adherentes a la DM (de acuerdo con la mejoría en el puntaje de la encuesta). Conclusiones: los niveles séricos de CML disminuyeron tras la restricción calórica con una dieta tipo mediterránea. Dado que no se pudo alcanzar la puntuación máxima en la encuesta de DM, no podemos concluir si la propia DM tiene un efecto aditivo a la restricción calórica.

  11. Genetic analysis of advanced glycation end products in the DHS MIND study.

    Science.gov (United States)

    Adams, Jeremy N; Raffield, Laura M; Martelle, Susan E; Freedman, Barry I; Langefeld, Carl D; Carr, J Jeffrey; Cox, Amanda J; Bowden, Donald W

    2016-06-15

    Advanced glycation end-products (AGEs) are a diverse group of molecules produced by the non-enzymatic addition of glucose to proteins, lipids, and nucleic acids. AGE levels have been associated with hyperglycemia and diabetic complications, especially in animal models, but less clearly in human studies. We measured total serum AGEs using an enzyme linked immunosorbant assay (ELISA) in 506 subjects from 246 families in the Diabetes Heart Study (DHS)/DHS MIND Study (n=399 type 2 diabetes (T2D)-affected). Single nucleotide polymorphisms (SNPs) in several candidate genes, including known AGE receptors, were tested for their influence on circulating AGE levels. The genetic analysis was expanded to include an exploratory genome-wide association study (GWAS) and exome chip analysis of AGEs (≈440,000 SNPs). AGEs were found to be highly heritable (h(2)=0.628, p=8.96 × 10(-10)). While no SNPs from candidate genes were significantly associated after Bonferroni correction, rs1035798 in the gene AGER was the most significantly associated (p=0.007). Additionally, rs7198427, in MT1A, showed a nominally significant p-value (p=0.0099). No SNPs from the GWAS or exome studies were identified after correction for multiple comparisons; however, rs17054480 in the PALLD2 gene on chromosome 4 showed the strongest association (p=7.77 × 10(-7)). Five SNPs at two loci (ISCA2/NPC2 and FBXO33) had p-values of less than 2.0 × 10(-5) and three additional SNPs (rs716326 in MACROD2, and rs6795197 and rs6765857 in ZBTB38) showed a nominal association with p-values of less than 1.0 × 10(-5).These findings provide a foundation for further investigation into the genetic component of circulating AGEs. PMID:26915486

  12. Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease

    NARCIS (Netherlands)

    Hartog, JWL; De Vries, APJ; Lutgers, HL; Meerwaldt, R; Huisman, RM; Van Son, WJ; De Jong, PE; Smit, AJ; Baynes, JW; Monnier, VM; Ames, JM; Thorpe,

    2005-01-01

    Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age,

  13. Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet

    OpenAIRE

    URIBARRI, JAIME; WOODRUFF, SANDRA; Goodman, Susan; Cai, Weijing; Chen, Xue; Pyzik, Renata; YONG, ANGIE; STRIKER, GARY E.; Vlassara, Helen

    2010-01-01

    Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and...

  14. Adverse effects of advanced glycation end products on embryonal development

    Directory of Open Access Journals (Sweden)

    Hiramatsu,Yuji

    2008-04-01

    Full Text Available We studied the effects of advanced glycation end products (AGEs, which are known to accumulate in patients with diabetes, autoimmune diseases, or those who smoke, on embryonal development. Pronuclear (PN embryos were obtained by flushing the fallopian tubes of rats after superovulation and mating. The cleavage rate and blastocyst yield were evaluated at 24, 72, 96, and 120 h of culture. Glyoxal, an AGE-forming aldehyde, suppressed embryonal development at every stage from PN to blastocyst in a concentration-dependent manner. The cleavage rate of the embryo was also signifi cantly decreased by treatment with glyoxal at concentrations of 1 mM or higher. The blastocyst yield was significantly decreased by treatment with glyoxal at concentrations of 0.5 mM or higher. N-acetyl-L-cysteine (L-NAC at 1 mM significantly suppressed the glyoxal-induced embryonal toxicity. BSA-AGEs at 5 microg/ml or higher concentration signifi cantly reduced the cleavage rate and blastocyst yield compared to those for BSA-treated embryos. L-NAC at 1 mM significantly suppressed BSAAGE-induced embryonal toxicity. Because AGEs are embryo-toxic, AGE contamination may influence the pregnancy rate of in vitro fertilization and embryo transfer. AGEs, which are increased in women under pathological conditions, may also be involved in their infertility.

  15. Determination of glycated hemoglobin in patients with advanced liver disease

    Institute of Scientific and Technical Information of China (English)

    Theresa Lahousen; Karin Hegenbarth; Rottraut Ille; Rainer W. Lipp; Robert Krause; Randie R. Little; Wolfgang J. Schnedl

    2004-01-01

    AIM: To evaluate the glycated hemoglobin (HbA1c)determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin.METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods.Fructosamine was determined using nitroblue tetrazolium.RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis)had HbA1c results below the non-diabetic reference range by at least one HbA1c method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA1c results were below the non-diabetic reference using at least one of the HbA1c methods.CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA1c results should be used in patients with advanced liver disease. HbA1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment.

  16. RAGE, receptor of advanced glycation endoproducts, negatively regulates chondrocytes differentiation.

    Directory of Open Access Journals (Sweden)

    Tatsuya Kosaka

    Full Text Available RAGE, receptor for advanced glycation endoproducts (AGE, has been characterized as an activator of osteoclastgenesis. However, whether RAGE directly regulates chondrocyte proliferation and differentiation is unclear. Here, we show that RAGE has an inhibitory role in chondrocyte differentiation. RAGE expression was observed in chondrocytes from the prehypertrophic to hypertrophic regions. In cultured cells, overexpression of RAGE or dominant-negative-RAGE (DN-RAGE demonstrated that RAGE inhibited cartilaginous matrix production, while DN-RAGE promoted production. Additionally, RAGE regulated Ihh and Col10a1 negatively but upregulated PTHrP receptor. Ihh promoter analysis and real-time PCR analysis suggested that downregulation of Cdxs was the key for RAGE-induced inhibition of chondrocyte differentiation. Overexpression of the NF-κB inhibitor I-κB-SR inhibited RAGE-induced NF-κB activation, but did not influence inhibition of cartilaginous matrix production by RAGE. The inhibitory action of RAGE was restored by the Rho family GTPases inhibitor Toxin B. Furthermore, inhibitory action on Ihh, Col10a1 and Cdxs was reproduced by constitutively active forms, L63RhoA, L61Rac, and L61Cdc42, but not by I-κB-SR. Cdx1 induced Ihh and Col10a1 expressions and directly interacted with Ihh promoter. Retinoic acid (RA partially rescued the inhibitory action of RAGE. These data combined suggests that RAGE negatively regulates chondrocyte differentiation at the prehypertrophic stage by modulating NF-κB-independent and Rho family GTPases-dependent mechanisms.

  17. Preserving brain function in aging: The anti-glycative potential of berry fruit

    Science.gov (United States)

    Advanced glycation end-products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produc...

  18. Involvement of Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury

    Science.gov (United States)

    Chiang, Chih-Kang; Wang, Ching-Chia; Lu, Tien-Fong; Huang, Kuo-How; Sheu, Meei-Ling; Liu, Shing-Hwa; Hung, Kuan-Yu

    2016-01-01

    Advanced glycation end-products (AGEs)-induced mesangial cell death is one of major causes of glomerulus dysfunction in diabetic nephropathy. Both endoplasmic reticulum (ER) stress and autophagy are adaptive responses in cells under environmental stress and participate in the renal diseases. The role of ER stress and autophagy in AGEs-induced mesangial cell death is still unclear. Here, we investigated the effect and mechanism of AGEs on glomerular mesangial cells. AGEs dose-dependently decreased mesangial cell viability and induced cell apoptosis. AGEs also induced ER stress signals in a time- and dose-dependent manner. Inhibition of ER stress with 4-phenylbutyric acid effectively inhibited the activation of eIF2α and CHOP signals and reversed AGEs-induced cell apoptosis. AGEs also activated LC-3 cleavage, increased Atg5 expression, and decreased p62 expression, which indicated the autophagy induction in mesangial cells. Inhibition of autophagy by Atg5 siRNAs transfection aggravated AGEs-induced mesangial cell apoptosis. Moreover, ER stress inhibition by 4-phenylbutyric acid significantly reversed AGEs-induced autophagy, but autophagy inhibition did not influence the AGEs-induced ER stress-related signals activation. These results suggest that AGEs induce mesangial cell apoptosis via an ER stress-triggered signaling pathway. Atg5-dependent autophagy plays a protective role. These findings may offer a new strategy against AGEs toxicity in the kidney. PMID:27665710

  19. An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2013-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia. Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications, the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreatic β-cell dysfunction. This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

  20. Reference values for the Chinese population of skin autofluorescence as a marker of advanced glycation end products accumulated in tissue

    NARCIS (Netherlands)

    Yue, X.; Hu, H.; Koetsier, M.; Graaff, R.; Han, C.

    2011-01-01

    Aim Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the

  1. Effects of bicarbonate/lactate solution on peritoneal advanced glycosylation end-product accumulation.

    Science.gov (United States)

    Park, M S; Kim, J K; Holmes, C; Weiss, M F

    2000-01-01

    Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However

  2. Guarana (Paullinia cupana Mart.) prevents β-amyloid aggregation, generation of advanced glycation-end products (AGEs), and acrolein-induced cytotoxicity on human neuronal-like cells.

    Science.gov (United States)

    Bittencourt, Leonardo da Silva; Zeidán-Chuliá, Fares; Yatsu, Francini Kiyono Jorge; Schnorr, Carlos Eduardo; Moresco, Karla Suzana; Kolling, Eduardo Antônio; Gelain, Daniel Pens; Bassani, Valquiria Linck; Moreira, José Cláudio Fonseca

    2014-11-01

    Advanced glycation end-products (AGEs) are considered potent molecules capable of promoting neuronal cell death and participating in the development of neurodegenerative disorders such as Alzheimer's disease (AD). Previous studies have shown that AGEs exacerbate β-amyloid (Aβ) aggregation and AGE-related cross-links are also detected in senile plaques. Acrolein (ACR) is an α, β-unsaturated aldehyde found in the environment and thermally processed foods, which can additionally be generated through endogenous metabolism. The role of ACR in AD is widely accepted in the literature. Guarana (Paullinia cupana Mart.) is popularly consumed by the population in Brazil, mainly for its stimulant activity. In the present study, we showed that guarana (10, 100, and 1000 µg/mL) is able to prevent protein glycation, β-amyloid aggregation, in vitro methylglyoxal, glyoxal, and ACR (20 μM)-induced toxicity on neuronal-like cells (SH-SY5Y). Since these are considered typical AD pathological hallmarks, we propose that guarana may deserve further research as a potential therapeutic agent in such a neurodegenerative disease. PMID:24840232

  3. Effect of collagen turnover on the accumulation of advanced glycation end products

    NARCIS (Netherlands)

    Verzijl, N.; Groot, J. de; Thorpe, S.R.; Bank, R.A.; Shaw, J.N.; Lyons, T.J.; Bijlsma, J.W.J.; Lafeber, F.P.J.G.; Baynes, J.W.; TeKoppele, J.M.

    2000-01-01

    Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidin

  4. Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia

    NARCIS (Netherlands)

    den Hollander, N. C.; Mulder, Douwe J.; Graaff, R.; Thorpe, S. R.; Baynes, J. W.; Smit, Gerrit; Smit, Andries

    2007-01-01

    Introducton: Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from

  5. Receptor for advanced glycation end product expression in experimental diabetic retinopathy

    NARCIS (Netherlands)

    Wang, Yumei; Hagen, Filanziska Vom; Pfister, Frederick; Bierhaus, Angelika; Feng, Yuxi; Gans, Reinhold; Hammes, Hans-Peter; Schleicher, E; Somoza,; Shieberle, P

    2008-01-01

    The advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway is involved in the pathogenesis of diabetic microvascular damage. The special distribution of RAGE and its engagement has an impact on the development of diabetic retinopathy. In the present study, we used immunofluorescence an

  6. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

    DEFF Research Database (Denmark)

    Forbes, Josephine M; Sourris, Karly C; de Courten, Maximilian;

    2013-01-01

    It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an...

  7. The Contribution of Advanced Glycation End product (AGE) accumulation to the decline in motor function

    NARCIS (Netherlands)

    Drenth, Hans; Zuidema, Sytse; Bunt, Steven; Bautmans, Ivan; van der Schans, Cees; Hobbelen, Hans

    2016-01-01

    Diminishing motor function is commonly observed in the elderly population and is associated with a wide range of adverse health consequences. Advanced Glycation End products (AGE's) may contribute to age-related decline in the function of cells and tissues in normal ageing. Although the negative eff

  8. The Contribution of advanced glycation End product (AGE) accumulation to the decline in motor function

    NARCIS (Netherlands)

    Drenth, Hans; Zuidema, Sytse; Bunt, Steven; Bautmans, Ivan; Schans, Cees van der; Hobbelen, Hans

    2016-01-01

    Diminishing motor function is commonly observed in the elderly population and is associated with a wide range of adverse health consequences. Advanced Glycation End products (AGE’s) may contribute to age-related decline in the function of cells and tissues in normal ageing. Although the negative eff

  9. Newer insights in drugs inhibiting formation and accumulation of advanced glycation end products.

    Directory of Open Access Journals (Sweden)

    Sana Alam

    2013-07-01

    Full Text Available It is now well established that non enzymatic glycation leads to formation of Amadori products which over course of time leads to formation of advanced glycation end products (AGEs. Accumulation of AGEs is very toxic and can have direct and indirect effects in the pathogenesis of various diseases including diabetes, alzheimer’s disease, rheumatoid arthritis etc. Hence, to curb these harmful effects, a number of natural and synthetic compounds are being investigated so as to reduce clinically the impact of AGEs. Here, various AGE inhibitors and breakers published till date are being reviewed. Also, potential novel therapies are also being explored.

  10. A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

    OpenAIRE

    Zhang, Qibin; Ames, Jennifer M; Smith, Richard D.; Baynes, John W.; Metz, Thomas O.

    2009-01-01

    The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the ...

  11. Advanced glycation end products induce differential structural modifications and fibrillation of albumin

    Science.gov (United States)

    Awasthi, Saurabh; Sankaranarayanan, Kamatchi; Saraswathi, N. T.

    2016-06-01

    Glycation induced amyloid fibrillation is fundamental to the development of many neurodegenerative and cardiovascular complications. Excessive non-enzymatic glycation in conditions such as hyperglycaemia results in the increased accumulation of advanced glycation end products (AGEs). AGEs are highly reactive pro-oxidants, which can lead to the activation of inflammatory pathways and development of oxidative stress. Recently, the effect of non-enzymatic glycation on protein structure has been the major research area, but the role of specific AGEs in such structural alteration and induction of fibrillation remains undefined. In this study, we determined the specific AGEs mediated structural modifications in albumin mainly considering carboxymethyllysine (CML), carboxyethyllysine (CEL), and argpyrimidine (Arg-P) which are the major AGEs formed in the body. We studied the secondary structural changes based on circular dichroism (CD) and spectroscopic analysis. The AGEs induced fibrillation was determined by Congo red binding and examination of scanning and transmission electron micrographs. The amyloidogenic regions in the sequence of BSA were determined using FoldAmyloid. It was observed that CEL modification of BSA leads to the development of fibrillar structures, which was evident from both secondary structure changes and TEM analysis.

  12. Effect of dietary advanced glycation end products on postprandial appetite, inflammation, and endothelial activation in healthy overweight individuals

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Bak, Monika Judyta; Andersen, Jeanette Marker;

    2014-01-01

    Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress.......Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress....

  13. Novel Inhibitory Effects of Glycyrrhizic Acid on the Accumulation of Advanced Glycation End Product and Its Receptor Expression

    OpenAIRE

    Cheng, Hong Sheng; Kong, Joana Magdelene Xiao Fang; Ng, Athena Xin Hui; Chan, Weng Keong; Ton, So Ha; Abdul Kadir, Khalid

    2014-01-01

    Abstract Beneficial effects of glycyrrhizic acid (GA), a bioactive extract of licorice root, in the prevention of metabolic syndrome have been consistently reported while advanced glycation end products (AGE) and receptor for advanced glycation end product (RAGE) are the leading factors in the development of diabetes mellitus. The aim of this study was to investigate the effects of GA on the AGE-RAGE axis using high-fat/high-sucrose (HF/HS) diet-induced metabolic syndrome rat models. Twenty f...

  14. Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Louise J. N. Jensen

    2015-01-01

    Full Text Available The receptor of advanced glycation end products (RAGE and its ligands are linked to the pathogenesis of coronary artery disease (CAD, and circulating soluble receptor of advanced glycation end products (sRAGE, reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS. The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently.

  15. Receptor for Advanced Glycation End Products Regulates Adipocyte Hypertrophy and Insulin Sensitivity in Mice

    OpenAIRE

    Monden, Masayo; Koyama, Hidenori; Otsuka, Yoshiko; Morioka, Tomoaki; Mori, Katsuhito; Shoji, Takuhito; Mima, Yohei; Motoyama, Koka; Fukumoto, Shinya; Shioi, Atsushi; Emoto, Masanori; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Nishizawa, Yoshiki; Kurajoh, Masafumi

    2013-01-01

    Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown o...

  16. The Receptor for Advanced Glycation End Products Is a Central Mediator of Asthma Pathogenesis

    OpenAIRE

    Pavle S Milutinovic; Alcorn, John F.; Englert, Judson M; Crum, Lauren T.; Oury, Tim D.

    2012-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been shown to contribute to the pathogenesis of diabetes, atherosclerosis, and neurodegeneration. However, its role in asthma and allergic airway disease is largely unknown. These studies use a house dust mite (HDM) mouse model of asthma/allergic airway disease. Respiratory mechanics were assessed and compared between wild-type and RAGE knockout mice. Bronchovascular architecture was assessed with quant...

  17. Paradoxical function for the receptor for advanced glycation end products in mouse models of pulmonary fibrosis

    OpenAIRE

    Englert, Judson M; Kliment, Corrine R.; Ramsgaard, Lasse; Pavle S Milutinovic; Crum, Lauren; Tobolewski, Jacob M.; Oury, Tim D.

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression of the receptor for advanced glycation end products (RAGE) in the lung is significantly decreased in human IPF lungs and in two animal models of pulmonary fibrosis. In addition, RAGE-null mice spontaneously develop pulmonary fibrosis with age and more severe fibrosis when challenged with asbestos. ...

  18. Advanced glycation end products induce fibrogenic activity in NASH by modulating the TNFα converting enzyme activity

    OpenAIRE

    Joy, Jiang X; Chen, Xiangling; Fukada, Hiroo; Serizawa, Nobuko; Devaraj, Sridevi; Török, Natalie J.

    2013-01-01

    Advanced glycation end products (AGEs) accumulate in patients with diabetes, yet the link between AGEs and the inflammatory and fibrogenic activity in non-alcoholic steatohepatitis (NASH) has not been explored. TNFα converting enzyme (TACE) is at the center of inflammatory processes. As the main natural regulator of TACE activity is the tissue inhibitor of metalloproteinase 3 (Timp3), we hypothesized that AGEs induce TACE through NADPH oxidase 2 (NOX2); and the downregulation of Sirtuin 1 (Si...

  19. Advanced glycation end products measured by skin autofluorescence in a population with central obesity

    OpenAIRE

    den Engelsen, Corine; van den Donk, Maureen; Gorter, Kees J; Salomé, Philippe L; Rutten, Guy E

    2012-01-01

    Accumulation of advanced glycation end products (AGEs) is enhanced by chronic hyperglycemia and oxidative stress and this process may contribute to the pathogenesis of vascular disease. Skin autofluorescence (AF), a measure of accumulation of AGEs in skin collagen, is associated with vascular disease in patients with diabetes.   Because central obesity enhances oxidative stress people with central obesity might already have increased accumulation of AGEs before diabetes or cardiovascular dise...

  20. Assessment of advanced glycated end product accumulation in skin using auto fluorescence multispectral imaging

    OpenAIRE

    Larsson, Marcus; Favilla, Riccardo; Strömberg, Tomas

    2015-01-01

    Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF).A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, ...

  1. The Contribution of Advanced Glycation End product (AGE) accumulation to the decline in motor function

    OpenAIRE

    Drenth, Hans; Zuidema, Sytse; Bunt, Steven; Bautmans, Ivan; Schans, Cees van der; Hobbelen, Hans

    2016-01-01

    Diminishing motor function is commonly observed in the elderly population and is associated with a wide range of adverse health consequences. Advanced Glycation End products (AGE’s) may contribute to age-related decline in the function of cells and tissues in normal ageing. Although the negative effect of AGE’s on the biomechanical properties of musculoskeletal tissues and the central nervous system have been previously described, the evidence regarding the effect on motor function is fragmen...

  2. Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles

    DEFF Research Database (Denmark)

    Knott, Heather M; Brown, Bronwyn E; Davies, Michael Jonathan;

    2003-01-01

    Patients with diabetes mellitus suffer from an increased incidence of complications including cardiovascular disease and cataracts; the mechanisms responsible for this are not fully understood. One characteristic of such complications is an accumulation of advanced glycation end-products formed b...

  3. Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study

    Science.gov (United States)

    Szkudlarek, A.; Maciążek-Jurczyk, M.; Chudzik, M.; Równicka-Zubik, J.; Sułkowska, A.

    2016-01-01

    The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by 1H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation.

  4. Advanced Glycation End Products, Inflammation, and Chronic Metabolic Diseases: Links in a Chain?

    Science.gov (United States)

    Davis, Kathleen E; Prasad, Chandan; Vijayagopal, Parakat; Juma, Shanil; Imrhan, Victorine

    2016-01-01

    Advanced glycation end products (AGEs) are a diverse group of compounds produced when reducing sugars react with proteins or other compounds to form glycosylated molecules. AGEs may form endogenously, and glycation of molecules may negatively affect their function. AGEs may also be consumed in food form with dietary AGEs reported to be particularly high in foods treated with high heat: baked, broiled, grilled, and fried foods. Whether dietary AGEs are absorbed in significant quantities and whether they are harmful if absorbed is a question under current debate. The American Diabetes Association makes no recommendation regarding avoidance of these foods, but many researchers are concerned that they may be pro-inflammatory and way worsen cardiac function, kidney function, diabetes and its complications and may even contribute to obesity. PMID:25259686

  5. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy

    NARCIS (Netherlands)

    Meerwaldt, R; Links, TP; Graaff, R; Hoogenberg, K; Lefrandt, JD; Baynes, JW; Gans, ROB; Smit, AJ

    2005-01-01

    Aims/hypothesis: The accumulation of AGE is related to the progression of the renal, retinal and vascular complications of diabetes. However, the relationship with diabetic neuropathy remains unclear. We recently showed that skin autofluorescence, measured non-invasively with an AutoFluorescence Rea

  6. Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

    DEFF Research Database (Denmark)

    Chen, Peng-Min; Gregersen, Hans; Zhao, Jingbo

    2015-01-01

    and five micron sections were cut. The layer thickness was measured in Hematoxylin and Eosin-stained slides. AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis...

  7. Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights

    OpenAIRE

    Priyanka Singh; Jayaramaiah, Ramesha H.; Sachin B. Agawane; Garikapati Vannuruswamy; Arvind M. Korwar; Atul Anand; Dhaygude, Vitthal S.; Mahemud L. Shaikh; Rakesh S Joshi; Ramanamurthy Boppana; Kulkarni, Mahesh J; Hirekodathakallu V. Thulasiram; Giri, Ashok P.

    2016-01-01

    Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand e...

  8. A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.; Baynes, John; Metz, Thomas O.

    2008-12-18

    The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide on overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

  9. Tea Flavanols Block Advanced Glycation of Lens Crystallins Induced by Dehydroascorbic Acid.

    Science.gov (United States)

    Zhu, Yingdong; Zhao, Yantao; Wang, Pei; Ahmedna, Mohamed; Ho, Chi-Tang; Sang, Shengmin

    2015-01-20

    Growing evidence has shown that ascorbic acid (ASA) can contribute to protein glycation and the formation of advanced glycation end products (AGEs), especially in the lens. The mechanism by which ascorbic acid can cause protein glycation probably originates from its oxidized form, dehydroascorbic acid (DASA), which is a reactive dicarbonyl species. In the present study, we demonstrated for the first time that four tea flavanols, (-)-epigallocatechin 3-O-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin 3-O-gallate (ECG), and (-)-epicatechin (EC), could significantly trap DASA and consequently form 6C- or 8C-ascorbyl conjugates. Among these four flavanols, EGCG exerted the strongest trapping efficacy by capturing approximate 80% of DASA within 60 min. We successfully purified and identified seven 6C- or 8C-ascorbyl conjugates of flavanols from the chemical reaction between tea flavanols and DASA under slightly basic conditions. Of which, five ascorbyl conjugates, EGCGDASA-2, EGCDASA-2, ECGDASA-1, ECGDASA-2 and ECDASA-1, were recognized as novel compounds. The NMR data showed that positions 6 and 8 of the ring A of flavanols were the major active sites for trapping DASA. We further demonstrated that tea flavanols could effectively inhibit the formation of DASA-induced AGEs via trapping DASA in the bovine lens crystallin-DASA assay. In this assay, 8C-ascorbyl conjugates of flavanols were detected as the major adducts using LC-MS. This study suggests that daily consumption of beverages containing tea flavanols may prevent protein glycation in the lens induced by ascorbic acid and its oxidized products. PMID:25437149

  10. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.

  11. Determinants of concentrations of N(ε)-carboxymethyl-lysine and soluble receptor for advanced glycation end products and their associations with risk of pancreatic cancer.

    Science.gov (United States)

    Duan, Zhigang; Chen, Guoqing; Chen, Liang; Stolzenberg-Solomon, Rachael; Weinstein, Stephanie J; Mannisto, Satu; White, Donna L; Albanes, Demetrius; Jiao, Li

    2014-01-01

    The soluble receptor for advanced glycation end-products (sRAGE) is shown to mitigate pro-inflammatory effects triggered by ligation of RAGE with N(ε)-carboxymethyl-lysine (CML)-AGE or other ligands. We examined the associations among host, lifestyle, and genetic determinants of CML-AGE or sRAGE and risk of pancreatic cancer in the prospective ATBC Study. We obtained baseline exposure information, data on serological and genetic biomarkers from 141 patients with pancreatic cancer and 141 subcohort controls. Stepwise linear and logistic regression models were used for data analysis. Multiple linear regression analyses showed that CML-AGE concentrations were independently inversely correlated with the minor allele of rs640742 of DDOST, physical activity, alcohol consumption, diastolic blood pressure (BP), and positively correlated with heart rate, serum sRAGE and HDL concentrations (P RAGE, age, body mass index, heart rate, and serum HDL; and positively correlated with serum CML-AGE, sucrose consumption, and diastolic BP (P RAGE was associated with reduced risk of pancreatic cancer (any T compared with CC: multivariate OR = 0.61, 95% CI: 0.38-0.98). We identified host metabolic profile, lifestyle and genetic factors that explained approximately 50% of variability of CML-AGE or sRAGE in Finnish men smokers. The association between RAGE SNPs and pancreatic cancer risk warrants further investigation. PMID:25379135

  12. Effects of photobleaching on selected advanced glycation end products in the human lens

    DEFF Research Database (Denmark)

    Holm, Thomas; Raghavan, Cibin T; Nahomi, Rooban;

    2015-01-01

    BackgroundCataract is the leading cause of blindness, especially in the developing world. To ease access to treatment, we have proposed that cataract could be treated non-invasively by photobleaching of the chemically modified proteins responsible for cataract formation. The present study was aimed...... at examining the optical and biochemical effects of the proposed treatment.MethodsHuman donor lenses were photobleaced using a 445 nm cw laser. Lens optical quality was assessed before and after photobleaching by light transmission and scattering. The concentration of the advanced glycation end products (AGEs...

  13. Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes

    OpenAIRE

    Liu, Feng-Cheng; Hung, Li-Feng; Wu, Wan-Lin; Chang, Deh-Ming; Huang, Chuan-Yueh; Lai, Jenn-Haung; Ho, Ling-Jun

    2010-01-01

    Introduction Accumulation of advanced glycation end products (AGEs) in joints contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We aim to explore the potential chondroprotective effects of resveratrol on AGEs-stimulated porcine chondrocytes and cartilage explants. Methods Chondrocytes were isolated from pig joints. Activation of the IκB kinase (IKK)-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)-activa...

  14. Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).

    Science.gov (United States)

    Han, Young Taek; Kim, Kyeojin; Choi, Gyeong-In; An, Hongchan; Son, Dohyun; Kim, Hee; Ha, Hee-Jin; Son, Jun-Hyeng; Chung, Suk-Jae; Park, Hyun-Ju; Lee, Jeewoo; Suh, Young-Ger

    2014-05-22

    In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described. PMID:24727489

  15. Evaluation of the Antioxidant and Anti-glication Effects of the Hexane Extract from Piper auritum Leaves in Vitro and Beneficial Activity on Oxidative Stress and Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Treated Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Adriana Maria Neira Gonzalez

    2012-10-01

    Full Text Available The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS. Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

  16. Evaluation of the antioxidant and anti-glication effects of the hexane extract from Piper auritum leaves in vitro and beneficial activity on oxidative stress and advanced glycation end-product-mediated renal injury in streptozotocin-treated diabetic rats.

    Science.gov (United States)

    Perez Gutierrez, Rosa Martha; Flores Cotera, Luis B; Gonzalez, Adriana Maria Neira

    2012-10-09

    The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS). Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE) formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

  17. Role of the receptor for advanced glycation end products in hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Christina Lohwasser; Daniel Neureiter; Yury Popov; Michael Bauer; Detlef Schuppan

    2009-01-01

    AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGEBSA) and Nε-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-α (TNF-α). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1(Ⅰ) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.

  18. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease.

    Science.gov (United States)

    Vos, Frederiek E; Schollum, John B; Walker, Robert J

    2011-12-01

    Diabetic nephropathy is the most common aetiology of end-stage kidney disease (ESKD). Strict glycaemic control reduces the development and progression of diabetes-related complications, and there is evidence that improved metabolic control improves outcomes in diabetic subjects with advanced chronic kidney disease (CKD). Glycaemic control in people with kidney disease is complex. Changes in glucose and insulin homeostasis may occur as a consequence of loss of kidney function and dialysis. The reliability of measures of long-term glycaemic control is affected by CKD and the accuracy of glycated haemoglobin (HbA1c) in the setting of CKD and ESKD is questioned. Despite the altered character of diabetes in CKD, current guidelines for diabetes management are not specifically adjusted to this patient group. The validity of indicators of longer term glycaemic control has been the focus of increased recent research. This review discusses the current understanding of commonly used indicators of metabolic control (HbA1c, fructosamine, glycated albumin) in the setting of advanced CKD (Stages 4 and 5, glomerular filtration rate <30 mL/min/1.73m(2)).

  19. Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA.

    Science.gov (United States)

    Zhu, Ping; Yang, Chuan; Chen, Li-Hong; Ren, Meng; Lao, Guo-Juan; Yan, Li

    2011-07-01

    The migration and proliferation of keratinocytes is critical to wound re-epithelialization and defects in this function are associated with the clinical phenomenon of chronic non-healing wounds. Advanced glycation end products (AGEs) occur through non-enzymatic glycation of long-lived proteins in diabetes and play important roles in diabetic complications. However, specific roles for AGEs in keratinocyte migration and proliferation, and the underlying molecular mechanisms, have not been fully established. The aim of the current study was to elucidate the interaction between AGE-modified bovine serum albumin (AGE-BSA) and keratinocytes. As a result, we found that AGE-BSA had no effect on the viability of keratinocytes for up to 48 h of incubation with 50 μg/ml of AGE-BSA. AGE-BSA (but not non-glycated BSA) exerted a concentration-dependent suppression of keratinocyte migration at a range of concentrations. The expression of matrix metalloproteinase-9 (MMP-9) was significantly up-regulated in keratinocytes incubated with increasing AGE-BSA, but tissue inhibitor of metalloproteinases-1 (TIMP-1) expression was down-regulated. AGE-BSA also profoundly depressed phospho-focal adhesion kinase-Tyr397 (p-FAK) and α2β1 integrin expression, while total-FAK expression levels remained constant, in keratinocytes. The proliferative capacity of keratinocytes was diminished after 72 h AGE-BSA incubation. Taken together, these findings suggested that in the presence of AGE-BSA, keratinocytes lose their migratory and proliferation abilities. These data also indicated that, in the context of the chronic hyperglycemia in diabetes, the effects of AGE-BSA on keratinocyte migration might be mediated through MMP-9/TIMP-1, p-FAK and α2β1 integrin.

  20. [Glycation of extracellular matrix proteins and its role in atherosclerosis].

    Science.gov (United States)

    Kuzan, Aleksandra; Chwiłkowska, Agnieszka; Kobielarz, Magdalena; Pezowicz, Celina; Gamian, Andrzej

    2012-10-29

    Glycation consists in formation of advanced glycation end-products (AGE) during non-enzymatic reaction between reducing sugars and proteins, lipids or nucleic acids. This review is focused mainly on glycation of collagen and its role in acceleration of vascular disease. Collagen is an extracellular matrix protein characterized by unique structure forming fibrils with great anti-tensile and anti-breaking strength. The protein builds the connective tissue and is responsible for biomechanical properties of blood vessels. It is reported that higher content of glycated collagen correlates with lower elasticity and greater toughness of the vessel walls and, as a consequence, a faster rate of atherosclerosis development. Numerous mechanisms connected with AGE formation are involved in atherogenesis, among others: receptor-mediated production of free radicals, triggering an inflammatory process, activation of leukocytes and thrombocytes, facilitation of LDL binding, change in level of growth factors, adhesion molecules, MMP and some other proteins' expression. The coverages allow the development of therapeutic strategies to prevent or slow down the pathological processes connected with glycation of collagen and other proteins in the artery wall. The main strategies are based on limitation of exogenous AGE, consumption of products which contain rutin, treatment with drugs which inhibit AGE formation, such as pyridoxamine, and chemicals which are able to cleave already formed AGE protein-protein crosslinks, such as ALT-711.

  1. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27Kip1, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  2. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products.

    Science.gov (United States)

    Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

    2015-11-12

    The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow's feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation.

  3. Accumulation of advanced glycation end products and chronic complications in ESRD treated by dialysis.

    Science.gov (United States)

    Meerwaldt, Robbert; Zeebregts, Clark J; Navis, Gerjan; Hillebrands, Jan-Luuk; Lefrandt, Joop D; Smit, Andries J

    2009-01-01

    Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease (ESRD), and the accumulation of advanced glycation end products (AGEs) is significantly increased in these patients. Accumulation of AGEs is believed to have a role in tissue protein aging and the pathogenesis of such age-related diseases as diabetes and ESRD. AGEs accumulate in patients with ESRD as a result of nonenzymatic glycation, oxidative stress, and diminished clearance of AGE precursors. Some AGEs show characteristic brown pigmentation and fluorescence, form protein-protein cross-links, and may ligate with AGE-specific receptors, inducing oxidative stress and cytokine production. This review focuses on the clinical relevance of AGE accumulation in patients with ESRD treated by dialysis for the development of long-term complications. The formation and accumulation of AGEs in patients with ESRD are discussed, as well as the relationship between AGE accumulation and such major complications of ESRD as cardiovascular and connective tissue disorders.

  4. Skin autofluorescence as a measure of advanced glycation end products deposition is elevated in peripheral artery disease

    NARCIS (Netherlands)

    De Vos, Lisanne C.; Noordzij, Marjon J.; Mulder, Douwe J.; Smit, Andries J.; Lutgers, Helen L.; Dullaart, Robin P.F.; Kamphuisen, Pieter W.; Zeebregts, Clark J.; Lefrandt, Johan

    2013-01-01

    OBJECTIVE: Evidence for an important role of advanced glycation end products (AGEs) in the development of atherosclerosis and cardiovascular disease beyond diabetes mellitus and renal disease is growing. Skin autofluorescence (SAF) is a validated noninvasive measure of tissue AGEs. We hypothesized t

  5. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients

    NARCIS (Netherlands)

    Meerwaldt, R; Hartog, JWL; Graaff, R; Huisman, RJ; Links, TP; den Hollander, NC; Thorpe, [No Value; Baynes, JW; Navis, G; Gans, ROB; Smit, AJ

    2005-01-01

    Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, sk

  6. Accumulation of Advanced Glycation End Products as a Molecular Mechanism for Aging as a Risk Factor in Osteoarthritis

    NARCIS (Netherlands)

    Groot, J. de; Verzijl, N.; Wenting-Wijk, M.J.G. van; Jacobs, K.M.G.; El, B. van; Roermund, P.M. van; Bank, R.A.; Bijlsma, J.W.J.; TeKoppele, J.M.; Lafeber, F.P.J.G.

    2004-01-01

    Objective. Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. Its etiology is largely unknown, but age is the most prominent risk factor. The current study was designed to test whether accumulation of advanced glycation end products (AGEs), which

  7. Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Berg, T J; Snorgaard, O; Faber, J;

    1999-01-01

    Impairment of left ventricular diastolic function, possibly caused by increased collagen cross-linking of the cardiac muscle, is common in patients with type 1 diabetes even without coronary artery disease. Advanced glycation end products (AGEs) cross-link tissue collagen and are found within myo...

  8. Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

    DEFF Research Database (Denmark)

    Sourris, Karly C; Lyons, Jasmine G; Dougherty, Sonia L;

    2013-01-01

    Abstract Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to...

  9. Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation

    OpenAIRE

    A. Heidland; Šebeková, K.; Frangiosa, A; De Santo, L S; Cirillo, M.; Rossi, F.; Cotrufo, M.; Perna, A; Klassen, A; Schinzel, R; De Santo, N G

    2004-01-01

    Objectives: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated.

  10. Role of zinc along with ascorbic acid and folic acid during long-term in vitro albumin glycation.

    Science.gov (United States)

    Tupe, Rashmi Santosh; Agte, Vaishali Vilas

    2010-02-01

    The present study aimed to investigate the role of Zn alone and in the presence of ascorbic acid (AA) and folic acid (FA) in albumin glycation. Glycation was performed by incubations of bovine serum albumin with glucose at 37 degrees C along with Zn, AA or FA separately and Zn + AA or Zn + FA for 150 d. Glycation-mediated modifications were monitored as fluorescence of advanced glycation endproducts, carbonyl formation, beta aggregation (thioflavin T and Congo red dyes), albumin-bound Zn, thiol groups and glycated aggregate's toxicity in HepG2 cells. Zn inhibited glycation and beta aggregation, probably due to observed higher protein-bound Zn. It also protected protein thiols and increased cell survival. AA and FA enhanced glycation, which was lowered in Zn-co-incubated samples. FA increased albumin-bound Zn and showed maximum cell survival. Although these results warrant further in vivo investigation, the present data help in the understanding of the interplay of Zn with micronutrients in albumin glycation.

  11. Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease.

    Science.gov (United States)

    Hartog, Jasper W L; de Vries, Aiko P J; Lutgers, Helen L; Meerwaldt, Robbert; Huisman, Roel M; van Son, Willem J; de Jong, Paul E; Smit, Andries J

    2005-06-01

    Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dialysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients compared with normal control subjects (2.8 vs. 2.0 arbitrary units [a.u.], P Reader) to measure AGE accumulation may be used to monitor AGE accumulation in a clinical setting as well as in a study setting.

  12. Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease.

    Science.gov (United States)

    Hartog, Jasper W L; de Vries, Aiko P J; Lutgers, Helen L; Meerwaldt, Robbert; Huisman, Roel M; van Son, Willem J; de Jong, Paul E; Smit, Andries J

    2005-06-01

    Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dialysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients compared with normal control subjects (2.8 vs. 2.0 arbitrary units [a.u.], P Reader) to measure AGE accumulation may be used to monitor AGE accumulation in a clinical setting as well as in a study setting. PMID:16037252

  13. The receptor for advanced glycation end products (RAGE) and the lung.

    LENUS (Irish Health Repository)

    Buckley, Stephen T

    2010-01-01

    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.

  14. Receptor for Advanced Glycation End Products (RAGE) Deficiency Attenuates the Development of Atherosclerosis in Diabetes

    Science.gov (United States)

    Soro-Paavonen, Aino; Watson, Anna M.D.; Li, Jiaze; Paavonen, Karri; Koitka, Audrey; Calkin, Anna C.; Barit, David; Coughlan, Melinda T.; Drew, Brian G.; Lancaster, Graeme I.; Thomas, Merlin; Forbes, Josephine M.; Nawroth, Peter P.; Bierhaus, Angelika; Cooper, Mark E.; Jandeleit-Dahm, Karin A.

    2008-01-01

    OBJECTIVE—Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE−/− model of accelerated atherosclerosis. RESEARCH DESIGN AND METHODS—ApoE−/− and RAGE−/−/apoE−/− double knockout mice were rendered diabetic with streptozotocin and followed for 20 weeks, at which time plaque accumulation was assessed by en face analysis. RESULTS—Although diabetic apoE−/− mice showed increased plaque accumulation (14.9 ± 1.7%), diabetic RAGE−/−/apoE−/− mice had significantly reduced atherosclerotic plaque area (4.9 ± 0.4%) to levels not significantly different from control apoE−/− mice (4.3 ± 0.4%). These beneficial effects on the vasculature were associated with attenuation of leukocyte recruitment; decreased expression of proinflammatory mediators, including the nuclear factor-κB subunit p65, VCAM-1, and MCP-1; and reduced oxidative stress, as reflected by staining for nitrotyrosine and reduced expression of various NADPH oxidase subunits, gp91phox, p47phox, and rac-1. Both RAGE and RAGE ligands, including S100A8/A9, high mobility group box 1 (HMGB1), and the advanced glycation end product (AGE) carboxymethyllysine were increased in plaques from diabetic apoE−/− mice. Furthermore, the accumulation of AGEs and other ligands to RAGE was reduced in diabetic RAGE−/−/apoE−/− mice. CONCLUSIONS—This study provides evidence for RAGE playing a central role in the development of accelerated atherosclerosis associated with diabetes. These findings emphasize the potential utility of strategies targeting RAGE activation in the prevention and treatment of diabetic macrovascular complications. PMID:18511846

  15. Detection of advanced glycation end products (AGEs) on human skin by in vivo confocal Raman spectroscopy

    Science.gov (United States)

    Martin, A. A.; Pereira, L.; Ali, S. M.; Pizzol, C. D.; Tellez, C. A.; Favero, P. P.; Santos, L.; da Silva, V. V.; Praes, C. E. O.

    2016-03-01

    The aging process involves the reduction in the production of the major components of skin tissue. During intrinsic aging and photoaging processes, in dermis of human skin, fibroblasts become senescent and have decreased activity, which produce low levels of collagen. Moreover, there is accumulation of advanced glycation end products (AGEs). AGEs have incidence in the progression of age-related diseases, principally in diabetes mellitus and in Alzheimer's diseases. AGEs causes intracellular damage and/or apoptosis leading to an increase of the free radicals, generating a crosslink with skin proteins and oxidative stress. The aim of this study is to detect AGEs markers on human skin by in vivo Confocal Raman spectroscopy. Spectra were obtained by using a Rivers Diagnostic System, 785 nm laser excitation and a CCD detector from the skin surface down to 120 μm depth. We analyzed the confocal Raman spectra of the skin dermis of 30 women volunteers divided into 3 groups: 10 volunteers with diabetes mellitus type II, 65-80 years old (DEW); 10 young healthy women, 20-33 years old (HYW); and 10 elderly healthy women, 65-80 years old (HEW). Pentosidine and glucosepane were the principally identified AGEs in the hydroxyproline and proline Raman spectral region (1000-800 cm-1), in the 1.260-1.320 cm-1 region assignable to alpha-helical amide III modes, and in the Amide I region. Pentosidine and glucosepane calculated vibrational spectra were performed through Density Functional Theory using the B3LYP functional with 3-21G basis set. Difference between the Raman spectra of diabetic elderly women and healthy young women, and between healthy elderly women and healthy young women were also obtained with the purpose of identifying AGEs Raman bands markers. AGEs peaks and collagen changes have been identified and used to quantify the glycation process in human skin.

  16. 食品中高级糖基化终产物的研究进展%Research Progress of Advanced Glycation End-products(AGEs) in Foods

    Institute of Scientific and Technical Information of China (English)

    蔡成岗; 张慧; 李赫; 陆胤; 洪昱渂

    2013-01-01

    The conception, sources, adverse effects and detection methods of advanced glycation end-products (AGEs) in foods were reviewed. AGEs originated from reactions of sugar and proteins or lipids in foods processed in high temperature, have adverse effects on disease of cardiovascular and diabetes, stimulate inflammation and aging. AGEs are composed of a diverse groups of compounds and usually analyzed by HPLC and ELISA methods for the detection of several indicator chemicals of N-carboxymethyl-lysine and etc. Analysis of AGEs compounds will be benefical for the control of food processing and food safety ensuring.%综述食品中高级糖基化终产物的概念、来源、危害和在部分食品中的检测方法。高级糖基化终产物为糖和蛋白质或脂肪反应生成,在食品中主要存在于高温加热烹制的食品,具有促进炎症、心血管疾病、糖尿病和加速衰老等有害作用,结构复杂。检测中常以羧甲基赖氨酸等为指标,采用高效液相色谱和酶联免疫的方法进行分析。高级糖基化终产物的检测分析对于食品加工工艺控制和饮食安全保障具有重要的作用。

  17. Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products.

    Science.gov (United States)

    Hegele, Jörg; Buetler, Timo; Delatour, Thierry

    2008-06-01

    Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N(epsilon)-fructoselysine (FL), N(epsilon)-carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34+/-3.81 nmol CML per micromol of free Lys (Lys(free)) and 81.5+/-87.8 nmol Pyr micromol(-1) Lys(free)(-1) vs. 3.72+/-1.29 nmol FL micromol(-1) Lys(free)(-1). In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47+/-0.08 nmol FL micromol(-1) of protein-bound Lys (Lys(p-b)), 0.04+/-0.03 nmol CML micromol(-1) Lys(p-b)(-1) and 0.06+/-0.02 nmol Pyr micromol(-1)Lys(p-b)(-1). It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products.

  18. Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity, and to conjugate methylglyoxal.

    Science.gov (United States)

    Shen, Yixiao; Xu, Zhimin; Sheng, Zhanwu

    2017-02-01

    Glycation can generate advanced glycation end products (AGE) and its intermediates methylglyoxal (MGO) and glyoxal in foods, which increase the risk of developing diabetes diseases. In this study, the effect of resveratrol against AGE formation, carbohydrate-hydrolyzing enzyme activity and trapping MGO capability were evaluated. Resveratrol showed a significant inhibition capability against AGE formation in bovine serum albumin (BSA)-fructose, BSA-MGO and arginine-MGO models with inhibition percentages of 57.94, 85.95 and 99.35%, respectively. Furthermore, resveratrol acted as a competitive inhibitor for α-amylase with IC50 3.62μg/ml, while it behaved in an uncompetitive manner for α-glucosidase with an IC50 of 17.54μg/l. A prevention of BSA protein glycation was observed in the BSA-fructose model with addition of resveratrol. Three types of resveratrol-MGO adducts were identified in the model consisting of MGO and resveratrol. The results demonstrated that resveratrol has potential in reducing glycation in foods and retarding carbohydrate-hydrolyzing enzyme activities. PMID:27596404

  19. Effects of non-enzymatic glycation in human serum albumin. Spectroscopic analysis

    Science.gov (United States)

    Szkudlarek, A.; Sułkowska, A.; Maciążek-Jurczyk, M.; Chudzik, M.; Równicka-Zubik, J.

    2016-01-01

    Human serum albumin (HSA), transporting protein, is exposed during its life to numerous factors that cause its functions become impaired. One of the basic factors - glycation of HSA - occurs in diabetes and may affect HSA-drug binding. Accumulation of advanced glycation end-products (AGEs) leads to diseases e.g. diabetic and non-diabetic cardiovascular diseases, Alzheimer disease, renal disfunction and in normal aging. The aim of the present work was to estimate how non-enzymatic glycation of human serum albumin altered its tertiary structure using fluorescence technique. We compared glycated human serum albumin by glucose (gHSAGLC) with HSA glycated by fructose (gHSAFRC). We focused on presenting the differences between gHSAFRC and nonglycated (HSA) albumin used acrylamide (Ac), potassium iodide (KI) and 2-(p-toluidino)naphthalene-6-sulfonic acid (TNS). Changes of the microenvironment around the tryptophan residue (Trp-214) of non-glycated and glycated proteins was investigated by the red-edge excitation shift method. Effect of glycation on ligand binding was examined by the binding of phenylbutazone (PHB) and ketoprofen (KP), which a primary high affinity binding site in serum albumin is subdomain IIA and IIIA, respectively. At an excitation and an emission wavelength of λex 335 nm and λem 420 nm, respectively the increase of fluorescence intensity and the blue-shift of maximum fluorescence was observed. It indicates that the glycation products decreases the polarity microenvironment around the fluorophores. Analysis of red-edge excitation shift method showed that the red-shift for gHSAFRC is higher than for HSA. Non-enzymatic glycation also caused, that the Trp residue of gHSAFRC becomes less accessible for the negatively charged quencher (I-), KSV value is smaller for gHSAFRC than for HSA. TNS fluorescent measurement demonstrated the decrease of hydrophobicity in the glycated albumin. KSV constants for gHSA-PHB systems are higher than for the unmodified serum

  20. Influence of Physical Activity Intervention on Circulating Soluble Receptor for Advanced Glycation end Products in Elderly Subjects

    OpenAIRE

    Kotani, Kazuhiko; Caccavello, Russell; Sakane, Naoki; Yamada, Toshiyuki; Taniguchi, Nobuyuki; Gugliucci, Alejandro

    2011-01-01

    Background Inflammation, often accompanied by oxidation, caused by advanced glycation end products (AGEs) may be quenched by the soluble receptor for AGEs (sRAGE). The present study aimed to investigate the influence of physical activity on circulating sRAGE, and the association between changes of circulating sRAGE and paraoxonase1 (PON1) activity (as an antioxidative enzyme) in a physical activity intervention study on an elderly subject cohort. Methods Serum sRAGE, PON1 activity and cardiom...

  1. Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management

    OpenAIRE

    Palimeri S; Palioura E; Diamanti-Kandarakis E

    2015-01-01

    Sotiria Palimeri,* Eleni Palioura,* Evanthia Diamanti-KandarakisEndocrine Unit, Medical School University of Athens, Athens, Greece*These authors contributed equally to this workAbstract: Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxi...

  2. Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Berg, T J; Snorgaard, O; Faber, J;

    1999-01-01

    Impairment of left ventricular diastolic function, possibly caused by increased collagen cross-linking of the cardiac muscle, is common in patients with type 1 diabetes even without coronary artery disease. Advanced glycation end products (AGEs) cross-link tissue collagen and are found within...... myocardial fibers. The aim of this study was to examine for a possible association between circulating AGEs and left ventricular cardiac function....

  3. Distinct associations of HbA(1c) and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    Smulders, R.A.; Stehouwer, C.D.A.; Schalkwijk, C.G.; Donker, A.J.M.; Hinsbergh, V.W.M. van; TeKoppele, J.M.

    1998-01-01

    Dysfunction of the vascular endothelium is considered an early step in the development of diabetic angiopathy. Hyperglycaemia results in endothelial dysfunction, both through direct effects of glucose and through formation of advanced glycosylation end-products (AGEs). We hypothesized that the effec

  4. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    International Nuclear Information System (INIS)

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction

  5. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    Science.gov (United States)

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-12-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80 ± 5.50%, PBSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  6. Advanced glycation end products (AGEs and their receptor (RAGE induce apoptosis of periodontal ligament fibroblasts

    Directory of Open Access Journals (Sweden)

    D.X. Li

    2014-12-01

    Full Text Available Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL fibroblasts induced by advanced glycation end products (AGEs and their receptor (RAGE. We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA, bovine serum albumin (BSA alone, or given no treatment (control. Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01 and increased apoptosis (11.31±1.73%, P<0.05. Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  7. The Receptor for Advanced Glycation End Products Activates the AIM2 Inflammasome in Acute Pancreatitis.

    Science.gov (United States)

    Kang, Rui; Chen, Ruochan; Xie, Min; Cao, Lizhi; Lotze, Michael T; Tang, Daolin; Zeh, Herbert J

    2016-05-15

    Severe acute pancreatitis (AP) is responsible for significant human morbidity and mortality worldwide. Currently, no specific treatments for AP exist, primarily due to the lack of a mechanistic understanding of sterile inflammation and the resultant multisystem organ dysfunction, the pathologic response of AP linked to early death. In this study, we demonstrate that the class III major histocompatibility region III receptor for advanced glycation end products (RAGE) contributes to AP by modulating inflammasome activation in macrophages. RAGE mediated nucleosome-induced absent in melanoma 2 (but not NLRP3) inflammasome activation by modulating dsRNA-dependent protein kinase phosphorylation in macrophages. Pharmacological and genetic inhibition of the RAGE-dsRNA-dependent protein kinase pathway attenuated the release of inflammasome-dependent exosomal leaderless cytokines (e.g., IL-1β and high-mobility group box 1) in vitro. RAGE or absent in melanoma 2 depletion in mice limited tissue injury, reduced systemic inflammation, and protected against AP induced by l-arginine or cerulein in experimental animal models. These findings define a novel role for RAGE in the propagation of the innate immune response with activation of the nucleosome-mediated inflammasome and will help guide future development of therapeutic strategies to treat AP. PMID:27045109

  8. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J. [Department of Stomatology, Air Force General Hospital PLA, Haidian District, Beijing (China)

    2014-09-19

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  9. Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yaw Kuang Chuah

    2013-01-01

    Full Text Available The receptor for advanced glycation end products (RAGE is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.

  10. Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products.

    Directory of Open Access Journals (Sweden)

    Pavle S Milutinovic

    Full Text Available Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE. Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin.

  11. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs.

    Science.gov (United States)

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  12. Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Yu; Yu, Manli; Zhang, Le; Cao, Qingxin; Song, Ying; Liu, Yuxiu; Gong, Jianbin

    2016-08-01

    Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway. PMID:27426491

  13. Chemo-enzymatic synthesis of vinyl and l-ascorbyl phenolates and their inhibitory effects on advanced glycation end products.

    Science.gov (United States)

    Hwang, Seung Hwan; Wang, Zhiqiang; Lim, Soon Sung

    2017-01-01

    This study successfully established the feasibility of a two-step chemo-enzymatic synthesis of l-ascorbyl phenolates. Intermediate vinyl phenolates were first chemically produced and then underwent trans-esterification with l-ascorbic acid in the presence of Novozyme 435® (Candida Antarctica lipase B) as a catalyst. Twenty vinyl phenolates and 11 ascorbyl phenolates were subjected to in vitro bioassays to investigate their inhibitory activity against advanced glycation end products (AGEs). Among them, vinyl 4-hydroxycinnamate (17VP), vinyl 4-hydroxy-3-methoxycinnamate (18VP), vinyl 4-hydroxy-3,5-dimethoxycinnamate (20VP), ascorbyl 4-hydroxy-3-methoxycinnamate (18AP) and ascorbyl 3,4-dimethoxycinnamate (19AP) showed 2-10 times stronger inhibitory activities than positive control (aminoguanidine and its precursors). These results indicated that chemo-enzymatically synthesized compounds have AGE inhibitory effect and thus are effective in either preventing or retarding glycation protein formation. PMID:27507531

  14. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells.

    Science.gov (United States)

    Li, Ziqing; Li, Chaohong; Zhou, Yuhuan; Chen, Weishen; Luo, Guotian; Zhang, Ziji; Wang, Haixing; Zhang, Yangchun; Xu, Dongliang; Sheng, Puyi

    2016-03-01

    Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW264.7 cell-derived osteoclast-like cells (OCLs). AGE-modified BSA (50-400 μg/ml) or control BSA (100 μg/ml) was then added at the beginning of each stage. Results showed that the presence of AGEs at the cell fusion stage reduced pit numbers, resorption area, and CTSK expression. Moreover, expression of receptor activator of nuclear factor-κB (RANK) as well as the number of TRAP-positive cells, nuclei per OCL, actin rings, and podosomes also decreased. However, the presence of AGEs at the mature stage enlarged the resorption area markedly and increased pit numbers slightly. Intriguingly, only the number of nuclei per OCL and podosomes increased. These data indicate that AGEs biphasically modulate bone resorption activity of OCLs in a differentiation stage-dependent manner. AGEs at the cell fusion stage reduce bone resorption dramatically, mainly via suppression of RANK expression in osteoclast precursors, whereas AGEs at the mature stage enhance bone resorption slightly, most likely by increasing the number of podosomes in mature OCLs.

  15. Garlic decreases liver and kidney receptor for advanced glycation end products expression in experimental diabetes.

    Science.gov (United States)

    Al-Qattan, Khaled K; Mansour, Mohamed H; Thomson, Martha; Ali, Muslim

    2016-06-01

    The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy and hepatic fibrogenesis. The present study was designed to investigate the potential of garlic (Allium sativum L.) to modulate the level of expression of RAGE in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal and hepatic tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in glomeruli exhibiting signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In the liver, a significant up-regulation of RAGE was observed in hepatocytes and bile ducts and vessels in portal tracts. In 2-dimensional Western blots, RAGE expression in both tissues was dominated by heterogeneous charge variants, represented by 46-50kDa isoforms with more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal and hepatic regions and was marked by the expression of 43-50kDa acidic charge variants comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders. PMID:26968224

  16. Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products.

    Directory of Open Access Journals (Sweden)

    Afshin Iram

    Full Text Available Conformational alterations of bovine hemoglobin (Hb upon sequential addition of glyoxal over a range of 0-90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT fluorescence and red shifted Congo Red (CR absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's.

  17. Advanced glycation end product associated skin autofluorescence: a mirror of vascular function?

    Science.gov (United States)

    Hofmann, Britt; Adam, Anne-Catrin; Jacobs, Kathleen; Riemer, Marcus; Erbs, Christian; Bushnaq, Hasan; Simm, Andreas; Silber, Rolf-Edgar; Santos, Alexander Navarrete

    2013-01-01

    Advanced glycation end products (AGEs) seem to be involved in aging as well as in the development of cardiovascular diseases. During aging, AGEs accumulate in extracellular matrix proteins like collagen and contribute to vessel stiffness. Whether non-invasive measurement of AGE accumulation in the skin may reflect vessel function and vessel protein modification is unknown. Herein we set out to analyze the AGE-modifications in the collagens extracted from residual bypass graft material, the skin autofluorescence reflecting the accumulation of AGEs in the body as well as the pulse wave velocity reflecting vessel stiffness. Collagen types I and III (pepsin digestible collagen fraction) were isolated from the veins of 52 patients by proteolysis. The residual collagen fraction was further extracted by collagenase digestion. Collagen was quantified by hydroxyproline assay and AGEs by the AGE intrinsic fluorescence. Skin autofluorescence was measured with an autofluorescence reader; pulse wave velocity with the VICORDER. The collagen AGE autofluorescence in patient vein graft material increased with patient age. The pepsin digestible collagen fraction was significantly less modified in comparison to the collagenase digestible fraction. Decreasing amounts of extracted collagenase digestible collagen correspond with increasing AGE autofluorescence. Skin autofluorescence and vessel stiffness were significantly linked to the AGE autofluorescence of the collagenase digestible collagen fraction from graft material. In conclusion we have found that skin autofluorescence and pulse wave velocity as non-invasive parameters significantly correlate with the AGE contained in graft material and therefore are strong predictors of vessel AGE modifications in patients with coronary heart disease. Whether the analysis of the skin autofluorescence leads to an improvement of the risk stratification in patients suffering from cardiovascular disease has to be further tested.

  18. Advanced glycation end products measured by skin autofluorescence in a population with central obesity.

    Science.gov (United States)

    den Engelsen, Corine; van den Donk, Maureen; Gorter, Kees J; Salomé, Philippe L; Rutten, Guy E

    2012-01-01

    Accumulation of advanced glycation end products (AGEs) is enhanced by chronic hyperglycemia and oxidative stress and this process may contribute to the pathogenesis of vascular disease. Skin autofluorescence (AF), a measure of accumulation of AGEs in skin collagen, is associated with vascular disease in patients with diabetes.   Because central obesity enhances oxidative stress people with central obesity might already have increased accumulation of AGEs before diabetes or cardiovascular disease become manifest. To test this hypothesis, we compared the distribution of skin AF and its association with clinical and biochemical parameters in individuals with and without central obesity. Skin AF was measured by a validated AGE Reader in 816 persons with and 431 persons without central obesity, aged 20-70 y. Mean skin AF increased with age and smoking and was higher in centrally obese individuals compared with non-obese individuals (p = 0.001, after adjustment for age and smoking p = 0.13). Mean skin AF in the subgroups without central obesity and without other risk factors (n = 106), central obesity without other risk factors (n = 74) and central obesity with other risk factors (n = 742) was 1.63 ± 0.37, 1.74 ± 0.44 and 1.87 ± 0.43 AU, respectively (p for trend < 0.001, after adjustment for age and smoking p for trend = 0.12). In the group with central obesity age, current smoking, alcohol consumption, waist circumference, creatinine clearance and hs-CRP were independently associated with skin AF (R(2) = 29.4%). Waist circumference hardly contributed to the explained variance. The relationship between waist circumference and skin AF is not as obvious as we hypothesized.

  19. Advanced glycation end products and the progressive course of renal disease.

    Science.gov (United States)

    Heidland, A; Sebekova, K; Schinzel, R

    2001-10-01

    In experimental and human diabetic nephropathy (DN), it has been shown that advanced glycation end products (AGEs), in particular, carboxymethyl-lysine and pentosidine, accumulate with malondialdehyde in glomerular lesions in relation to disease severity and in the presence of an upregulated receptor for AGE (RAGE) in podocytes. Toxic effects of AGEs result from structural and functional alterations in plasma and extracellular matrix (ECM) proteins, in particular, from cross-linking of proteins and interaction of AGEs with their receptors and/or binding proteins. In mesangial and endothelial cells, the AGE-RAGE interaction caused enhanced formation of oxygen radicals with subsequent activation of nuclear factor-kappaB and release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), growth factors (transforming growth factor-beta1 [TGF-beta1], insulin-like growth factor-1), and adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). In tubular cells, incubation with AGE albumin was followed by stimulation of the mitogen-activating protein (MAP) kinase pathway and its downstream target, the activating protien-1 (AP-1) complex, TGF-beta1 overexpression, enhanced protein kinase C activity, decreased cell proliferation, and impaired protein degradation rate, in part caused by decreased cathepsin activities. The pathogenic relevance of AGEs was further verified by in vivo experiments in euglycemic rats and mice by the parenteral administration of AGE albumin, leading in the glomeruli to TGF-beta1 overproduction, enhanced gene expression of ECM proteins, and morphological lesions similar to those of DN. Evidence for the pathogenic relevance of AGEs in DN also comes from experimental studies in which the formation and/or action of AGEs was modulated by aminoguanidine, OPB-9195, pyridoxamine, soluble RAGEs, serine protease trypsin, and antioxidants, resulting in improved cell and/or renal function.

  20. Advanced glycation end products measured by skin autofluorescence in a population with central obesity.

    Science.gov (United States)

    den Engelsen, Corine; van den Donk, Maureen; Gorter, Kees J; Salomé, Philippe L; Rutten, Guy E

    2012-01-01

    Accumulation of advanced glycation end products (AGEs) is enhanced by chronic hyperglycemia and oxidative stress and this process may contribute to the pathogenesis of vascular disease. Skin autofluorescence (AF), a measure of accumulation of AGEs in skin collagen, is associated with vascular disease in patients with diabetes.   Because central obesity enhances oxidative stress people with central obesity might already have increased accumulation of AGEs before diabetes or cardiovascular disease become manifest. To test this hypothesis, we compared the distribution of skin AF and its association with clinical and biochemical parameters in individuals with and without central obesity. Skin AF was measured by a validated AGE Reader in 816 persons with and 431 persons without central obesity, aged 20-70 y. Mean skin AF increased with age and smoking and was higher in centrally obese individuals compared with non-obese individuals (p = 0.001, after adjustment for age and smoking p = 0.13). Mean skin AF in the subgroups without central obesity and without other risk factors (n = 106), central obesity without other risk factors (n = 74) and central obesity with other risk factors (n = 742) was 1.63 ± 0.37, 1.74 ± 0.44 and 1.87 ± 0.43 AU, respectively (p for trend < 0.001, after adjustment for age and smoking p for trend = 0.12). In the group with central obesity age, current smoking, alcohol consumption, waist circumference, creatinine clearance and hs-CRP were independently associated with skin AF (R(2) = 29.4%). Waist circumference hardly contributed to the explained variance. The relationship between waist circumference and skin AF is not as obvious as we hypothesized. PMID:22870350

  1. Advanced glycation end product associated skin autofluorescence: a mirror of vascular function?

    Science.gov (United States)

    Hofmann, Britt; Adam, Anne-Catrin; Jacobs, Kathleen; Riemer, Marcus; Erbs, Christian; Bushnaq, Hasan; Simm, Andreas; Silber, Rolf-Edgar; Santos, Alexander Navarrete

    2013-01-01

    Advanced glycation end products (AGEs) seem to be involved in aging as well as in the development of cardiovascular diseases. During aging, AGEs accumulate in extracellular matrix proteins like collagen and contribute to vessel stiffness. Whether non-invasive measurement of AGE accumulation in the skin may reflect vessel function and vessel protein modification is unknown. Herein we set out to analyze the AGE-modifications in the collagens extracted from residual bypass graft material, the skin autofluorescence reflecting the accumulation of AGEs in the body as well as the pulse wave velocity reflecting vessel stiffness. Collagen types I and III (pepsin digestible collagen fraction) were isolated from the veins of 52 patients by proteolysis. The residual collagen fraction was further extracted by collagenase digestion. Collagen was quantified by hydroxyproline assay and AGEs by the AGE intrinsic fluorescence. Skin autofluorescence was measured with an autofluorescence reader; pulse wave velocity with the VICORDER. The collagen AGE autofluorescence in patient vein graft material increased with patient age. The pepsin digestible collagen fraction was significantly less modified in comparison to the collagenase digestible fraction. Decreasing amounts of extracted collagenase digestible collagen correspond with increasing AGE autofluorescence. Skin autofluorescence and vessel stiffness were significantly linked to the AGE autofluorescence of the collagenase digestible collagen fraction from graft material. In conclusion we have found that skin autofluorescence and pulse wave velocity as non-invasive parameters significantly correlate with the AGE contained in graft material and therefore are strong predictors of vessel AGE modifications in patients with coronary heart disease. Whether the analysis of the skin autofluorescence leads to an improvement of the risk stratification in patients suffering from cardiovascular disease has to be further tested. PMID:22588061

  2. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Science.gov (United States)

    Achouiti, Ahmed; de Vos, Alex F; van 't Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W; Nawroth, Peter P; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A D

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID:26824892

  3. Receptor for Advanced Glycation End Products (RAGE Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Directory of Open Access Journals (Sweden)

    Ahmed Achouiti

    Full Text Available Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K. pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/- and normal wild-type (Wt mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS.

  4. Association between Advanced Glycation End Products and Impaired Fasting Glucose: Results from the SALIA Study.

    Directory of Open Access Journals (Sweden)

    Tom Teichert

    Full Text Available Advanced glycation end products (AGEs may contribute to the development of type 2 diabetes and related complications, whereas their role in the early deterioration of glycaemia is unknown. While previous studies used antibody-based methods to quantify AGEs, data from tandem mass spectrometry coupled liquid chromatography (LC-MS/MS-based measurements are limited to patients with known diabetes. Here, we used the LC-MS/MS method to test the hypothesis that plasma AGE levels are higher in individuals with impaired fasting glucose (IFG than in those with normal fasting glucose (NFG. Secondary aims were to assess correlations of plasma AGEs with quantitative markers of glucose metabolism and biomarkers of subclinical inflammation. This study included on 60 women with NFG or IFG (n = 30 each, mean age 74 years from the German SALIA cohort. Plasma levels of free metabolites (3-deoxyfructose, 3-deoxypentosone, 3-deoxypentulose, two hydroimidazolones, oxidised adducts (carboxymethyllysine, carboxyethyllysine, methionine sulfoxide and Nε-fructosyllysine were measured using LC-MS/MS. Plasma concentrations of all tested AGEs did not differ between the NFG and IFG groups (all p>0.05. Associations between plasma levels of AGEs and fasting glucose, insulin and HOMA-IR as a measure of insulin resistance were weak (r between -0.2 and 0.2, all p>0.05. The association between 3-deoxyglucosone-derived hydroimidazolone with several proinflammatory biomarkers disappeared upon adjustment for multiple testing. In conclusion, plasma AGEs assessed by LC-MS/MS were neither increased in IFG nor associated with parameters of glucose metabolism and subclinical inflammation in our study. Thus, these data argue against strong effects of AGEs in the early stages of deterioration of glucose metabolism.

  5. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

    Science.gov (United States)

    Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

    2016-10-01

    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

  6. Higher plasma soluble Receptor for Advanced Glycation End Products (sRAGE) levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes

    DEFF Research Database (Denmark)

    Nin, Johanna W M; Jorsal, Anders; Ferreira, Isabel;

    2010-01-01

    To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunct......To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal...

  7. Phlorotannins from Brown Algae: inhibition of advanced glycation end products formation in high glucose induced Caenorhabditis elegans.

    Science.gov (United States)

    Shakambari, Ganeshan; Ashokkumar, Balasubramaniem; Varalakshmi, Perumal

    2015-06-01

    Advanced Glycation End products (AGE) generated in a non enzymatic protein glycation process are frequently associated with diabetes, aging and other chronic diseases. Here, we explored the protective effect of phlorotannins from brown algae Padina pavonica, Sargassum polycystum and Turbinaria ornata against AGEs formation. Phlorotannins were extracted from brown algae with methanol and its purity was analyzed by TLC and RP-HPLC-DAD. Twenty five grams of P. pavonica, S. polycystum, T. ornata yielded 27.6 ± 0.8 μg/ml, 37.7 μg/ml and 37.1 ± 0.74 μg/ml of phloroglucinol equivalent of phlorotannins, respectively. Antioxidant potentials were examined through DPPH assay and their IC50 values were P. pavonica (30.12 ± 0.99 μg), S. polycystum (40.9 ± 1.2 μg) and T. ornata (22.9 ± 1.3 μg), which was comparatively lesser than the control ascorbic acid (46 ± 0.2 μg). Further, anti-AGE activity was examined in vitro by BSA-glucose assay with the extracted phlorotannins of brown algae (P. pavonica, 15.16 ± 0.26 μg/ml; S. polycystum, 35.245 ± 2.3 μg/ml; T. ornata, 22.7 ± 0.3 μg/ml), which revealed the required concentration to inhibit 50% of albumin glycation (IC50) were lower for extracts than controls (phloroglucinol, 222.33 ± 4.9 μg/ml; thiamine, 263 μg/ml). Furthermore, brown algal extracts containing phlorotannins (100 μl) exhibited protective effects against AGE formation in vivo in C. elegans with induced hyperglycemia. PMID:26155677

  8. Glucosamine-induced glycation of hydrolysed meat proteins in the presence or absence of transglutaminase: Chemical modifications and taste-enhancing activity.

    Science.gov (United States)

    Hong, Pui Khoon; Ndagijimana, Maurice; Betti, Mirko

    2016-04-15

    Salt reduction in food is a challenging task. The food processing sector has adopted taste enhancers to replace salt partially. In this study, a flavour enhancer formulation (liquid seasoning) was produced using enzymatically hydrolysed poultry proteins isolate (PPI). The PPI obtained through the isoelectric solubilisation precipitation process (ISP) was hydrolysed with Alcalase and glycated with glucosamine (GlcN) at moderate temperatures (37/50°C) in the presence or absence of transglutaminase (TGase). The glycated hydrolysates showed reduced fluorescence advanced glycated end-products (AGE) and a reduced amount of alpha-dicarbonyl compounds (α-DC). An untrained consumer panel ranked the meat protein hydrolysate seasoning saltier than the salty standard seasoning solution (psalty perception. PMID:26675851

  9. Analysis of advanced glycation endproducts in dairy products by isotope dilution liquid chromatography-electrospray tandem mass spectrometry. The particular case of carboxymethyllysine.

    Science.gov (United States)

    Delatour, Thierry; Hegele, Jörg; Parisod, Véronique; Richoz, Janique; Maurer, Sarah; Steven, Matthew; Buetler, Timo

    2009-03-20

    A fully validated multiple-transition recording isotope dilution liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitative determination of N(epsilon)-carboxymethyllysine (CML) and lysine in dairy products is described. Internal standards were [N-1',2'-(13)C(2)]CML and [1,2,3,4,5,6-(13)C(6)-2,6-(15)N(2)]lysine, and the method was validated by evaluating the selectivity, linearity, precision (repeatability and reproducibility) and trueness, using both powder and liquid products. For liquid dairy products, the repeatability and reproducibility was 2.79% and 11.0%, while 4.85% and 4.92% were determined for powder dairy products, respectively. The trueness of the method ranged from -9.6% to -3.6% for powder and from -0.99% to 6.8% for liquid dairy products. The limit of detection for CML was estimated to be 8 ng CML per mg protein while the limit of quantification was 27 ng CML per mg protein. The method encompasses a proteolytic cleavage mediated by enzymatic digestion to reach a complete release of the amino acids prior to a sample cleanup based on solid phase extraction, and followed by LC-MS/MS analysis of CML and lysine residues. To ensure a suitable performance of the enzymatic digestion, CML measurements were compared to values obtained with an acid hydrolysis-mediated proteolysis. Finally, the method was employed for the analysis of CML in various dairy products. The values compare well to the data available in the literature when similar methods were used, even if some discrepancies were observed upon comparison with the results obtained by other techniques such as enzyme-linked immunosorbent assay and GC-MS.

  10. Skin autofluorescence as a measure of tissue advanced glycation end products deposition is elevated in diabetic patients with peripheral artery disease

    NARCIS (Netherlands)

    De Vos, L.C.; Mulder, D.J.; Dullaart, R.P.F.; Lutgers, H.L.; Smit, A.J.; Kamphuisen, P.W.; Westra, Johanna; Zeebregts, C.J.; Lefrandt, J.D.

    2013-01-01

    Backgrounds and aims: Diabetes mellitus (DM) is an important risk factor for peripheral artery disease (PAD) and associated with a particularly poor prognosis in these patients. Increased glycemic and oxidative stress in DM enhance the accumulation of advanced glycation end products (AGEs), which pl

  11. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

    Science.gov (United States)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. PMID:27301641

  12. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

    Science.gov (United States)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly.

  13. Kinetics of advanced glycation end products formation on bovine serum albumin with various reducing sugars and dicarbonyl compounds in equimolar ratios.

    Science.gov (United States)

    Luers, Lars; Rysiewski, Karolina; Dumpitak, Christian; Birkmann, Eva

    2012-04-01

    Reducing sugars and reactive dicarbonyl compounds play a major role in glycation of proteins in vivo. Glycation of proteins is the first step in of a nonenzymatic reaction, resulting in advanced glycation end products (AGEs). AGEs can inactivate proteins or modify their biological activities. Therefore, it is important to understand the mechanism of AGE formation. Here, we systematically analyzed the kinetics of AGE formation in vitro by fluorescence and absorption measurements utilizing a microplate reader system and bovine serum albumin (BSA) as a model protein. Comparing different concentrations of BSA, we applied various reducing sugars and reactive dicarbonyl compounds as AGE-inducing agents at different concentrations. In summary, this experimental setup enabled us to measure the kinetics of AGE formation in an efficient and defined way.

  14. Kinetics of advanced glycation end products formation on bovine serum albumin with various reducing sugars and dicarbonyl compounds in equimolar ratios.

    Science.gov (United States)

    Luers, Lars; Rysiewski, Karolina; Dumpitak, Christian; Birkmann, Eva

    2012-04-01

    Reducing sugars and reactive dicarbonyl compounds play a major role in glycation of proteins in vivo. Glycation of proteins is the first step in of a nonenzymatic reaction, resulting in advanced glycation end products (AGEs). AGEs can inactivate proteins or modify their biological activities. Therefore, it is important to understand the mechanism of AGE formation. Here, we systematically analyzed the kinetics of AGE formation in vitro by fluorescence and absorption measurements utilizing a microplate reader system and bovine serum albumin (BSA) as a model protein. Comparing different concentrations of BSA, we applied various reducing sugars and reactive dicarbonyl compounds as AGE-inducing agents at different concentrations. In summary, this experimental setup enabled us to measure the kinetics of AGE formation in an efficient and defined way. PMID:22533432

  15. A Significant Inhibitory Effect on Advanced Glycation End Product Formation by Catechin as the Major Metabolite of Lotus Seedpod Oligomeric Procyanidins

    Directory of Open Access Journals (Sweden)

    Qian Wu

    2014-08-01

    Full Text Available Several lines of evidence suggested that B-type procyanidin oligomers from lotus seedpod (LSOPC may effectively modulate the formation of advanced glycation end products (AGEs. In vivo, LSOPC is metabolized by intestinal flora to become various kinds of phenolic compounds that possess potent antioxidant activities. However, few reports of the absorption and metabolism of LSOPC have been revealed. In the present study, rats were orally administered with LSOPC at a dose of 300 mg/kg body weight. The metabolites of LSOPC in urine were elucidated by HPLC-MS/MS analysis 24 h post-administration. Eight major metabolites were significantly increased by the administration of 300 mg/kg of LSOPC (p < 0.01. The anti-glycative activity of LSOPC and its metabolites were investigated. The results showed that LSOPC and catechin had greater anti-glycative activities than other metabolites, which were positively correlated to their carbonyl scavenging activities and antioxidant capacities.

  16. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: A possible mechanism through which age is a risk factor for osteoarthritis

    NARCIS (Netherlands)

    Verzijl, N.; Groot, J. de; Zaken, C.B.; Braun-Benjamin, O.; Maroudas, A.; Bank, R.A.; Mizrahi, J.; Schalkwijk, C.G.; Thorpe, S.R.; Baynes, J.W.; Bijlsma, J.W.J.; Lafeber, F.P.J.G.; TeKoppele, J.M.

    2002-01-01

    Objective. Age is an important risk factor for osteoarthritis (OA). During aging, nonenzymatic glycation results in the accumulation of advanced glycation end products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking on the stiffness of the collagen network in human articular

  17. The distribution of advanced glycation end products and their receptor in the gastrointestinal tract in the rats

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Gregersen, Hans

    2012-01-01

    To investigate the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the gastrointestinal (GI) tract to provide a basis for further study of the association between AGE/RAGE and diabetic GI dysfunction. METHODS: The distribution of AGEs [N epsilon......-(carboxymethyl) lysine and N epsilon-(carboxyethyl) lysine] and RAGE were detected in the esopha-geal, gastric, duodenal, jejunal, ileal, colonic and rectal tissues of normal adult Wistar rats using immunohistochemistry. RESULTS: In the esophagus, AGEs and RAGE were mainly distributed in striated muscle cells...... and squamous epithelial cells. In the stomach, AGEs were mainly distributed in parietal cells, and RAGE was strongly expressed in chief cells, mast cells and neurons in ganglia, moderately in parietal cells, and mildly in surface mucous cells. In the intestine, colon and rectum, AGEs and RAGE were distributed...

  18. Consumption of a diet low in advanced glycation end products for 4 weeks improves insulin sensitivity in overweight women

    DEFF Research Database (Denmark)

    Mark, Alicja Budek; Poulsen, Malene Wibe; Andersen, Stine;

    2014-01-01

    OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs. This parallel intervention study...... investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS Seventy-four overweight women were randomized to follow either a high- or low-AGE diet for 4 weeks, together with consumption...... AGE concentrations were measured (liquid chromatography tandem mass spectrometry) to estimate AGE intake and excretion. RESULTS When adjusted for changes in anthropometric measures during the intervention, the low-AGE diet decreased urinary AGEs, fasting insulin concentrations, and HOMA-IR, compared...

  19. Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

    Science.gov (United States)

    Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

    2011-04-01

    Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects.

  20. Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

    Science.gov (United States)

    Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

    2011-04-01

    Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects. PMID:20494372

  1. 3-Deoxyglucosone: a potential glycating agent accountable for structural alteration in H3 histone protein through generation of different AGEs.

    Directory of Open Access Journals (Sweden)

    Jalaluddin M Ashraf

    Full Text Available Advanced glycation end-products (AGEs are heterogeneous group of compounds, known to be implicated in diabetic complications. One of the consequences of the Maillard reaction is attributed to the production of reactive intermediate products such as α-oxoaldehydes. 3-deoxyglucosone (3-DG, an α-oxoaldehyde has been found to be involved in accelerating vascular damage during diabetes. In the present study, calf thymus histone H3 was treated with 3-deoxyglucosone to investigate the generation of AGEs (Nε-carboxymethyllysine, pentosidine, by examining the degree of side chain modifications and formation of different intermediates and employing various physicochemical techniques. The results clearly indicate the formation of AGEs and structural changes upon glycation of H3 by 3-deoxyglucosone, which may hamper the normal functioning of H3 histone, that may compromise the veracity of chromatin structures and function in secondary complications of diabetes.

  2. 糖基化终末产物及其受体在糖尿病大鼠胃组织中的分布 (Distribution of advanced glycation end products and their receptor in the stomach of diabetic rats)

    DEFF Research Database (Denmark)

    Tian, Jia Xing; Zhao, Jingbo; Li, Min;

    2015-01-01

    AIM: To observe the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the stomach of diabetic rats. METHODS: Diabetes mellitus (DM) and control (CON) rats were reared for eight weeks. Fasting plasma glucose (FPG), glycated serum protein (GSP) and gastric layer...... with the CON group (P stomach was significantly higher in the DM group than in the CON group (P ...: The expression of AGEs and RAGE is up-regulated in the stomach of diabetic rats. The increased levels of AGE and RAGE in gastric tissue may contribute to diabetic gastrointestinal dysfunction. © 2015 Baishideng Publishing Group Inc. All rights reserved. Key Words: Diabetes mellitus; Stomach; Advanced glycation...

  3. The receptor for advanced glycation end products (RAGE) affects T cell differentiation in OVA induced asthma.

    Science.gov (United States)

    Akirav, Eitan M; Henegariu, Octavian; Preston-Hurlburt, Paula; Schmidt, Ann Marie; Clynes, Raphael; Herold, Kevan C

    2014-01-01

    The receptor for glycation end products (RAGE) has been previously implicated in shaping the adaptive immune response. RAGE is expressed in T cells after activation and constitutively in T cells from patients with diabetes. The effects of RAGE on adaptive immune responses are not clear: Previous reports show that RAGE blockade affects Th1 responses. To clarify the role of RAGE in adaptive immune responses and the mechanisms of its effects, we examined whether RAGE plays a role in T cell activation in a Th2 response involving ovalbumin (OVA)-induced asthma in mice. WT and RAGE deficient wild-type and OT-II mice, expressing a T cell receptor specific for OVA, were immunized intranasally with OVA. Lung cellular infiltration and T cell responses were analyzed by immunostaining, FACS, and multiplex bead analyses for cytokines. RAGE deficient mice showed reduced cellular infiltration in the bronchial alveolar lavage fluid and impaired T cell activation in the mediastinal lymph nodes when compared with WT mice. In addition, RAGE deficiency resulted in reduced OT-II T cell infiltration of the lung and impaired IFNγ and IL-5 production when compared with WT mice and reduced infiltration when transferred into WT hosts. When cultured under conditions favoring the differentiation of T cells subsets, RAGE deficient T cells showed reduced production of IFNγ but increased production of IL-17. Our data show a stimulatory role for RAGE in T activation in OVA-induced asthma. This role is largely mediated by the effects of RAGE on T cell proliferation and differentiation. These findings suggest that RAGE may play a regulatory role in T cell responses following immune activation.

  4. Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-β-induced alveolar epithelial to mesenchymal transition

    OpenAIRE

    Song, Jeong Sup; Kang, Chun Mi; Park, Chan Kwon; Yoon, Hyung Kyu; Lee, Sook Young; Ahn, Joong Hyun; Moon, Hwa-Sik

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in...

  5. The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk: A Case-Control Study within the Prospective EPIC Cohort

    OpenAIRE

    Grote, Verena A; Nieters, Alexandra; Kaaks, Rudolf; Tjønneland, Anne; Roswall, Nina; Overvad, Kim; Nielsen, Michael R Skjelbo; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Racine, Antoine; Teucher, Birgit; Lukanova, Annekatrin; Boeing, Heiner; Drogan, Dagmar; Trichopoulou, Antonia

    2012-01-01

    BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic ca...

  6. UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

    Science.gov (United States)

    Linetsky, Mikhail; Raghavan, Cibin T.; Johar, Kaid; Fan, Xingjun; Monnier, Vincent M.; Vasavada, Abhay R.; Nagaraj, Ram H.

    2014-01-01

    Advanced glycation end products (AGEs) contribute to lens protein pigmentation and cross-linking during aging and cataract formation. In vitro experiments have shown that ascorbate (ASC) oxidation products can form AGEs in proteins. However, the mechanisms of ASC oxidation and AGE formation in the human lens are poorly understood. Kynurenines are tryptophan oxidation products produced from the indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway and are present in the human lens. This study investigated the ability of UVA light-excited kynurenines to photooxidize ASC and to form AGEs in lens proteins. UVA light-excited kynurenines in both free and protein-bound forms rapidly oxidized ASC, and such oxidation occurred even in the absence of oxygen. High levels of GSH inhibited but did not completely block ASC oxidation. Upon UVA irradiation, pigmented proteins from human cataractous lenses also oxidized ASC. When exposed to UVA light (320–400 nm, 100 milliwatts/cm2, 45 min to 2 h), young human lenses (20–36 years), which contain high levels of free kynurenines, lost a significant portion of their ASC content and accumulated AGEs. A similar formation of AGEs was observed in UVA-irradiated lenses from human IDO/human sodium-dependent vitamin C transporter-2 mice, which contain high levels of kynurenines and ASC. Our data suggest that kynurenine-mediated ASC oxidation followed by AGE formation may be an important mechanism for lens aging and the development of senile cataracts in humans. PMID:24798334

  7. Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management

    Directory of Open Access Journals (Sweden)

    Palimeri S

    2015-09-01

    Full Text Available Sotiria Palimeri,* Eleni Palioura,* Evanthia Diamanti-KandarakisEndocrine Unit, Medical School University of Athens, Athens, Greece*These authors contributed equally to this workAbstract: Advanced glycation end products (AGEs constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins. Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification.Keywords: AGEs, dietary glycotoxins, dietary restriction, PCOS, MSR-1, RAGE

  8. The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.

    Science.gov (United States)

    Ren, Xiang; Ma, Haiying; Qiu, Yuanyuan; Liu, Bo; Qi, Hui; Li, Zeyu; Kong, Hui; Kong, Li

    2015-08-01

    Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity.

  9. Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

    Directory of Open Access Journals (Sweden)

    Taketoshi Noguchi

    2010-01-01

    Full Text Available Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs and receptor for advanced glycation end products (RAGE and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins. Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.

  10. Contribution of the toxic advanced glycation end-productsreceptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-ichi; Takino; Kentaro; Nagamine; Takamitsu; Hori; Akiko; Sakasai-Sakai; Masayoshi; Takeuchi

    2015-01-01

    Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis(NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products(AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs(TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs(RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.

  11. Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients.

    Science.gov (United States)

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-08-01

    Advanced glycation end products (AGEs) are posttranslational modifications formed non-enzymatically from the reaction of carbohydrates and their degradation products with proteins. Accumulation of AGEs is associated with the progression of severe diabetic complications, for example, and elevated tissue levels of AGEs might even predict these pathologies. As AGE formation is often site-specific, mapping of these modification sites may reveal more sensitive and specific markers than the global tissue level. Here, 42 AGE modifications were identified in a bottom-up proteomic approach by tandem mass spectrometry, which corresponded to 36 sites in 22 high to medium abundant proteins in individual plasma samples obtained from type 2 diabetes mellitus (T2DM) patients with long disease duration (>10 years). Major modifications were glarg (11 modification sites) and carboxymethylation (5) of arginine and formylation (8), acetylation (7), and carboxymethylation (7) of lysine residues. Relative quantification of these sites in plasma samples obtained from normoglycemic individuals (n = 47) and patients with T2DM being newly diagnosed (n = 47) or of medium (2-5 years, n = 20) and long disease duration (>10 years, n = 20) did not reveal any significant differences. PMID:27236317

  12. The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.

    Science.gov (United States)

    Ren, Xiang; Ma, Haiying; Qiu, Yuanyuan; Liu, Bo; Qi, Hui; Li, Zeyu; Kong, Hui; Kong, Li

    2015-08-01

    Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity. PMID:26142569

  13. Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function

    Directory of Open Access Journals (Sweden)

    Ghada Elmhiri

    2014-01-01

    Full Text Available Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG, a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 μmol/l with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine. Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM, MG induced a significant (P<0.05 increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM, MG significantly inhibited insulin secretion (P<0.05. In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (P<0.05, while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (P<0.05. Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells.

  14. Regulation of Receptor for Advanced Glycation End Products (RAGE) Ectodomain Shedding and Its Role in Cell Function.

    Science.gov (United States)

    Braley, Alex; Kwak, Taekyoung; Jules, Joel; Harja, Evis; Landgraf, Ralf; Hudson, Barry I

    2016-06-01

    The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that can undergo proteolysis at the cell surface to release a soluble ectodomain. Here we observed that ectodomain shedding of RAGE is critical for its role in regulating signaling and cellular function. Ectodomain shedding of both human and mouse RAGE was dependent on ADAM10 activity and induced with chemical activators of shedding (ionomycin, phorbol 12-myristate 13-acetate, and 4-aminophenylmercuric acetate) and endogenous stimuli (serum and RAGE ligands). Ectopic expression of the splice variant of RAGE (RAGE splice variant 4), which is resistant to ectodomain shedding, inhibited RAGE ligand dependent cell signaling, actin cytoskeleton reorganization, cell spreading, and cell migration. We found that blockade of RAGE ligand signaling with soluble RAGE or inhibitors of MAPK or PI3K blocked RAGE-dependent cell migration but did not affect RAGE splice variant 4 cell migration. We finally demonstrated that RAGE function is dependent on secretase activity as ADAM10 and γ-secretase inhibitors blocked RAGE ligand-mediated cell migration. Together, our data suggest that proteolysis of RAGE is critical to mediate signaling and cell function and may therefore emerge as a novel therapeutic target for RAGE-dependent disease states. PMID:27022018

  15. [Glycation of lens proteins in diabetes and its non-invasive assessment - first experience in the Czech Republic].

    Science.gov (United States)

    Škrha, Jan; Šoupal, Jan; Prázný, Martin; Škrha, Jan

    2015-04-01

    Advanced glycation end-products (AGEs) play a crucial role in the pathogenesis of diabetes and its complications. Their accumulation in the lens reflects total glycation rate in the human body. Recently, a new confocal biomicroscope ClearPath DS-120 quickly measuring lens autofluorescence (LAF) has been developed. Our pilot study included 69 patients with diabetes and 49 healthy controls, in all subject LAF was measured and compared with skin autofluorescence (SAF) assessed by AGE-Reader. Both LAF (T1DM: 0,27 ± 0,09; T2DM: 0,22 ± 0,06; controls: 0,17 ± 0,04 AU; p glycated hemoglobin (HbA1c) was rather poor, since HbA1c cannot wholly reflect long-term glycation process. Lens autofluorescence could be a robust marker of long-term diabetes control predicting future complication risks. However, confirmation of such hypothesis will need other and long-term clinical studies.

  16. [Glycation of lens proteins in diabetes and its non-invasive assessment - first experience in the Czech Republic].

    Science.gov (United States)

    Škrha, Jan; Šoupal, Jan; Prázný, Martin; Škrha, Jan

    2015-04-01

    Advanced glycation end-products (AGEs) play a crucial role in the pathogenesis of diabetes and its complications. Their accumulation in the lens reflects total glycation rate in the human body. Recently, a new confocal biomicroscope ClearPath DS-120 quickly measuring lens autofluorescence (LAF) has been developed. Our pilot study included 69 patients with diabetes and 49 healthy controls, in all subject LAF was measured and compared with skin autofluorescence (SAF) assessed by AGE-Reader. Both LAF (T1DM: 0,27 ± 0,09; T2DM: 0,22 ± 0,06; controls: 0,17 ± 0,04 AU; p glycated hemoglobin (HbA1c) was rather poor, since HbA1c cannot wholly reflect long-term glycation process. Lens autofluorescence could be a robust marker of long-term diabetes control predicting future complication risks. However, confirmation of such hypothesis will need other and long-term clinical studies. PMID:25894266

  17. Role of Glyoxalase 1 (Glo1) and methylglyoxal (MG) in behavior: recent advances and mechanistic insights

    OpenAIRE

    Distler, Margaret G.; Palmer, Abraham A.

    2012-01-01

    Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MG), a cyotoxic byproduct of glycolysis that induces protein modification (advanced glycation end-products, AGEs), oxidative stress, and apoptosis. The concentration of MG is elevated under high-glucose conditions, such as diabetes. As such, GLO1 and MG have been implicated in the pathogenesis of diabetic complications. Recently, findings have linked GLO1 to numerous behavioral phenot...

  18. The effect of valsartan on the expression of the receptor for advanced glycation end products in human glomerular mesangial cells%缬沙坦对人肾小球系膜细胞糖基化终产物受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    钟林娜; 黄国良; 冯敏; 张莹

    2011-01-01

    目的:本实验探讨缬沙坦对糖基化终产物诱导的人肾小球系膜细胞氧化应激水平及糖基化终产物受体(RAGE)表达的影响.方法:体外常规培养人肾小球系膜细胞,运用糖基化修饰的牛血清白蛋白(AGE-BSA)和缬沙坦进行干预,流式细胞术检测细胞内活性氧(ROS),RT-PCR法检测NADPH氧化酶的亚基p47phox的mRNA表达,RT-PCR和细胞免疫化学法检测RAGE的表达量.结果:缬沙坦干预组人肾小球系膜细胞的ROS产生量、NADPH氧化酶的亚基p47phox mRNA表达量、RAGE表达量均低于AGE-BSA组(P<0.05),且缬沙坦的抑制作用呈浓度和时间依赖性.结论:缬沙坦可能通过降低氧化应激水平来抑制RAGE的表达.%Objective: To elucidate the effect of valsartan on human glomerular mesangial cells oxidative stress and the expression of the receptor for advanced glycation end products (RAGE) induced by the advanced glycation end-products (AGEs). Methods: Human glomerular mesangial cells were treated with advanced glycation end-product-bovine serum albumin (AGE-BSA) in the presence of valsartan. The reactive oxygen species( ROS) in cells were measured by Flow cytomeuy, and the mRNA of p47 phox, which was the primary subunits of NADPH oxi-dase, was detected by semi-quantitative reberse transcription polymerase chain reaction (RT-PCR). The mRNA of RAGE was detected by RT-PCR and the RAGE protein was assayed by immunocytochemistry. Results: The product of ROS, and the expression of p47 phox and RAGE in mesangial cells , which were treated with AGE-BSA in the presence of valsartan, were down-regulated compared with the groups treated with AGE-BSA(P < 0.05). Valsartan dose-dependently and ume-dependently inhibited the AGE-elicited overexpression of RAGE, ROS and p47phox in mesangial cells. Conclusion: Valsartan could inhibit RAGE expression through downregularion of oxidative stress.

  19. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients.

    Science.gov (United States)

    Meerwaldt, Robbert; Hartog, Jasper W L; Graaff, Reindert; Huisman, Roel J; Links, Thera P; den Hollander, Nynke C; Thorpe, Susan R; Baynes, John W; Navis, Gerjan; Gans, Rijk O B; Smit, Andries J

    2005-12-01

    Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P < 0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.

  20. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients.

    Science.gov (United States)

    Meerwaldt, Robbert; Hartog, Jasper W L; Graaff, Reindert; Huisman, Roel J; Links, Thera P; den Hollander, Nynke C; Thorpe, Susan R; Baynes, John W; Navis, Gerjan; Gans, Rijk O B; Smit, Andries J

    2005-12-01

    Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P < 0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation. PMID:16280473

  1. Advanced glycation end products promote hepatosteatosis by interfering with SCAP-SREBP pathway in fructose-drinking mice.

    Science.gov (United States)

    Mastrocola, Raffaella; Collino, Massimo; Rogazzo, Mara; Medana, Claudio; Nigro, Debora; Boccuzzi, Giuseppe; Aragno, Manuela

    2013-09-15

    Clinical studies have linked the increased consumption of fructose to the development of obesity, dyslipidemia, and impaired glucose tolerance, and a role in hepatosteatosis development is presumed. Fructose can undergo a nonenzymatic reaction from which advanced glycation end products (AGEs) are derived, leading to the formation of dysfunctional, fructosylated proteins; however, the in vivo formation of AGEs from fructose is still less known than that from glucose. In the present study C57Bl/6J mice received 15% (wt/vol) fructose (FRT) or 15% (wt/vol) glucose (GLC) in water to drink for 30 wk, resembling human habit to consume sugary drinks. At the end of the protocol both FRT- and GLC-drinking mice had increased fasting glycemia, glucose intolerance, altered plasma lipid profile, and marked hepatosteatosis. FRT mice had higher hepatic triglycerides deposition than GLC, paralleled by a greater increased expression and activity of the sterol regulatory element-binding protein 1 (SREBP1), the transcription factor responsible for the de novo lipogenesis, and of its activating protein SCAP. LC-MS analysis showed a different pattern of AGE production in liver tissue between FRT and GLC mice, with larger amount of carboxymethyl lysine (CML) generated by fructose. Double immunofluorescence and coimmunoprecipitation analysis revealed an interaction between CML and SCAP that could lead to prolonged activation of SREBP1. Overall, the high levels of CML and activation of SCAP/SREBP pathway associated to high fructose exposure here reported may suggest a key role of this signaling pathway in mediating fructose-induced lipogenesis.

  2. Generation of Soluble Advanced Glycation End Products Receptor (sRAGE)-Binding Ligands during Extensive Heat Treatment of Whey Protein/Lactose Mixtures Is Dependent on Glycation and Aggregation.

    Science.gov (United States)

    Liu, Fahui; Teodorowicz, Małgorzata; Wichers, Harry J; van Boekel, Martinus A J S; Hettinga, Kasper A

    2016-08-24

    Heating of protein- and sugar-containing materials is considered the primary factor affecting the formation of advanced glycation end products (AGEs). This study aimed to investigate the influence of heating conditions, digestion, and aggregation on the binding capacity of AGEs to the soluble AGE receptor (sRAGE). Samples consisting of mixtures of whey protein and lactose were heated at 130 °C. An in vitro infant digestion model was used to study the influence of heat treatment on the digestibility of whey proteins. The amount of sRAGE-binding ligands before and after digestion was measured by an ELISA-based sRAGE-binding assay. Water activity did not significantly affect the extent of digestibility of whey proteins dry heated at pH 5 (ranging from 3.3 ± 0.2 to 3.6 ± 0.1% for gastric digestion and from 53.5 ± 1.5 to 64.7 ± 1.1% for duodenal digestion), but there were differences in cleavage patterns of peptides among the samples heated at different pH values. Formation of sRAGE-binding ligands depended on the formation of aggregates and was limited in the samples heated at pH 5. Moreover, the sRAGE-binding activity of digested sample was changed by protease degradation and correlated with the digestibility of samples. In conclusion, generation of sRAGE-binding ligands during extensive heat treatment of whey protein/lactose mixtures is limited in acidic heating condition and dependent on glycation and aggregation. PMID:27460534

  3. Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue

    DEFF Research Database (Denmark)

    Couppé, Christian; Svensson, René B; Grosset, Jean-Francois;

    2014-01-01

    Life-long regular endurance exercise is known to counteract the deterioration of cardiovascular and metabolic function and overall mortality. Yet it remains unknown if life-long regular endurance exercise can influence the connective tissue accumulation of advanced glycation endproducts (AGEs......) that is associated with aging and lifestyle-related diseases. We therefore examined two groups of healthy elderly men: 15 master athletes (64 ± 4 years) who had been engaged in life-long endurance running and 12 old untrained (66 ± 4 years) together with two groups of healthy young men; ten young athletes matched...... counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurance running yields tendon tissue hypertrophy that may serve to lower the stress...

  4. Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response.

    Science.gov (United States)

    Han, Xiao-qun; Gong, Zuo-jiong; Xu, San-qing; Li, Xun; Wang, Li-kun; Wu, Shi-min; Wu, Jian-hong; Yang, Hua-fen

    2014-02-01

    This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It

  5. Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes

    Directory of Open Access Journals (Sweden)

    Paul Canning

    2007-01-01

    Full Text Available Breakdown of the inner blood-retinal barrier (iBRB occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3 in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT mice and in Gal-3−/− transgenic mice. Blood glucose was monitored and AGE levels were quantified by ELISA and immunohistochemistry. The diabetic groups were subdivided, and one group was treated with the AGE-inhibitor pyridoxamine (PM while separate groups of WT and Gal-3−/− mice were maintained as nondiabetic controls. iBRB integrity was assessed by Evans blue assay alongside visualisation of TJ protein complexes via occludin-1 immunolocalization in retinal flat mounts. Retinal expression levels of the vasopermeability factor VEGF were quantified using real-time RT-PCR and ELISA. WT diabetic mice showed significant AGE -immunoreactivity in the retinal microvasculature and also showed significant iBRB breakdown (P<.005. These diabetics had higher VEGF mRNA and protein expression in comparison to controls (P<.01. PM-treated diabetics had normal iBRB function and significantly reduced diabetes-mediated VEGF expression. Diabetic retinal vessels showed disrupted TJ integrity when compared to controls, while PM-treated diabetics demonstrated near-normal configuration. Gal-3−/− mice showed significantly less diabetes-mediated iBRB dysfunction, junctional disruption, and VEGF expression changes than their WT counterparts. The data suggests an AGE

  6. Advanced glycation end products inhibit testosterone secretion by rat Leydig cells by inducing oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Zhao, Yun-Tao; Qi, Ya-Wei; Hu, Chuan-Yin; Chen, Shao-Hong; Liu, You

    2016-08-01

    Diabetes severely impairs male reproduction. The present study assessed the effects and mechanisms of action of advanced glycation end products (AGEs), which play an important role in the development of diabetes complications, on testosterone secretion by rat Leydig cells. Primary rat Leydig cells were cultured and treated with AGEs (25, 50, 100 and 200 µg/ml). Testosterone production induced by human chorionic gonadotropin (hCG) was determined by ELISA. The mRNA and protein expression levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD), which are involved in testosterone biosynthesis, were measured by reverse transcription-quantitative PCR and western blot analyssi, respectively. Reactive oxygen species (ROS) production in Leydig cells was measured using the dichlorofluorescein diacetate (DCFH-DA) probe. The expression levels of endoplasmic reticulum stress-related proteins [C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78)] in the Leydig cells were measured by western blot analysis. We found that the AGEs markedly suppressed testosterone production by rat Leydig cells which was induced by hCG in a concentration-dependent manner compared with the control (PStAR, 3β-HSD and P450scc were downregulated by the AGEs in a dose-dependent manner compared with the control (P<0.01). The antioxidant agent, N-acetyl‑L‑cysteine (NAC), and the endoplasmic reticulum stress inhibitor, tauroursodeoxycholic acid (TUDCA), reversed the inhibitory effects of AGEs. In addition, the content of ROS in Leydig cells treated with AGEs increased significantly. The expression levels of CHOP and GRP78 were markedly upregulated by the AGEs in the Leydig cells. From these findings, it can be concluded that AGEs inhibit testosterone production by rat Leydig cells by inducing oxidative stress and endoplasmic reticulum stress. PMID:27315604

  7. Activation of Akt by advanced glycation end products (AGEs: involvement of IGF-1 receptor and caveolin-1.

    Directory of Open Access Journals (Sweden)

    Su-Jung Yang

    Full Text Available Diabetes is characterized by chronic hyperglycemia, which in turn facilitates the formation of advanced glycation end products (AGEs. AGEs activate signaling proteins such as Src, Akt and ERK1/2. However, the mechanisms by which AGEs activate these kinases remain unclear. We examined the effect of AGEs on Akt activation in 3T3-L1 preadipocytes. Addition of AGEs to 3T3-L1 cells activated Akt in a dose- and time-dependent manner. The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(PH oxidase inhibitor DPI, suggesting the involvement of Src and NAD(PH oxidase in the activation of PI3-kinase-Akt pathway by AGEs. AGEs-stimulated Src tyrosine phosphorylation was inhibited by NAC, suggesting that Src is downstream of NAD(PH oxidase. The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R kinase inhibitor AG1024. Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1 levels with siRNAs. Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. These results suggest that AGEs activate NAD(PH oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1

  8. Advanced glycation end products accelerate ischemia/reperfusion injury through receptor of advanced end product/nitrative thioredoxin inactivation in cardiac microvascular endothelial cells.

    Science.gov (United States)

    Liu, Yi; Ma, Yanzhuo; Wang, Rutao; Xia, Chenhai; Zhang, Rongqing; Lian, Kun; Luan, Ronghua; Sun, Lu; Yang, Lu; Lau, Wayne B; Wang, Haichang; Tao, Ling

    2011-10-01

    The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population.

  9. Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Long Shi

    Full Text Available Advanced Glycation End Products (AGEs has been implicated in the progression of diabetic keratopathy. However, details regarding their function are not well understood. In the present study, we investigated the effects of intracellular reactive oxygen species (ROS and JNK, p38 MAPK on AGE-modified bovine serum albumin (BSA induced Human telomerase-immortalized corneal epithelial cells (HUCLs apoptosis. We found that AGE-BSA induced HUCLs apoptosis and increased Bax protein expression, decreased Bcl-2 protein expression. AGE-BSA also induced the expression of receptor for advanced glycation end product (RAGE. AGE-BSA-RAGE interaction induced intracellular ROS generation through activated NADPH oxidase and increased the phosphorylation of p47phox. AGE-BSA induced HUCLs apoptosis was inhibited by pretreatment with NADPH oxidase inhibitors, ROS quencher N-acetylcysteine (NAC or neutralizing anti-RAGE antibodies. We also found that AGE-BSA induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked AGE-BSA-induced HUCLs apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by AGE-BSA. Our results indicate that AGE-BSA induced HUCLs apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.

  10. Evaluating the extent of protein damage in dairy products: simultaneous determination of early and advanced glycation-induced lysine modifications.

    Science.gov (United States)

    Hegele, Jörg; Parisod, Véronique; Richoz, Janique; Förster, Anke; Maurer, Sarah; Krause, René; Henle, Thomas; Bütler, Timo; Delatour, Thierry

    2008-04-01

    An isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine lysine (Lys), N(epsilon)-fructosyllysine (FL), N epsilon-carboxymethyllysine (CML), and pyrraline (Pyr) in dairy products. The presented approach entails protein cleavage via enzymatic digestion to liberate the aforementioned compounds, which were then quantified using a stable isotope dilution assay. LC-MS/MS analysis was performed by positive electrospray ionization recording two transition reactions per analyte in selected reaction monitoring mode. The CML and Lys values obtained with enzymatic digestion were compared to those acquired with acid hydrolysis HCl (6 mol/L), and the two proteolysis methods yielded comparable quantifications. Allowing for the fact that the investigated compounds are formed during different stages of the glycation process, the method is able to reveal the progress of protein glycation in dairy products.

  11. Glycation Reactions of Casein Micelles.

    Science.gov (United States)

    Moeckel, Ulrike; Duerasch, Anja; Weiz, Alexander; Ruck, Michael; Henle, Thomas

    2016-04-13

    After suspensions of micellar casein or nonmicellar sodium caseinate had been heated, respectively, in the presence and absence of glucose for 0-4 h at 100 °C, glycation compounds were quantitated. The formation of Amadori products as indicators for the "early" Maillard reaction were in the same range for both micellar and nonmicellar caseins, indicating that reactive amino acid side chains within the micelles are accessible for glucose in a comparable way as in nonmicellar casein. Significant differences, however, were observed concerning the formation of the advanced glycation end products (AGEs), namely, N(ε)-carboxymethyllysine (CML), pyrraline, pentosidine, and glyoxal-lysine dimer (GOLD). CML could be observerd in higher amounts in nonmicellar casein, whereas in the micelles the pyrraline formation was increased. Pentosidine and GOLD were formed in comparable amounts. Furthermore, the extent of protein cross-linking was significantly higher in the glycated casein micelles than in the nonmicellar casein samples. Dynamic light scattering and scanning electron microscopy showed that glycation has no influence on the size of the casein micelles, indicating that cross-linking occurs only in the interior of the micelles, but altered the surface morphology. Studies on glycation and nonenzymatic cross-linking can contribute to the understanding of the structure of casein micelles. PMID:27018258

  12. The Extract of Litsea japonica Reduced the Development of Diabetic Nephropathy via the Inhibition of Advanced Glycation End Products Accumulation in db/db Mice

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    Eunjin Sohn

    2013-01-01

    Full Text Available Increasing evidence indicates that advanced glycation end products (AGEs contribute to the pathogenesis of diabetic nephropathy. The aim of this study was to investigate the protective effect of L. japonica extract (LJE against renal damage in the db/db mouse. LJE (100 or 250 mg/kg per day was given to diabetic mice for 12 weeks. Body weight, blood glucose levels, glycated hemoglobin (HbA1c levels, and proteinuria were examined. In in vitro assay of the inhibition of AGE formation, immunohistochemical analysis of podocyte loss and AGE accumulations were performed. In 20-week-old db/db mice, severe hyperglycemia developed, and proteinuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. LJE treatment significantly reduced proteinuria and AGE accumulations in diabetic mice. Moreover, the loss of nephrin, an important slit diaphragm component in the kidneys, was restored by LJE treatment. Our studies suggest that LJE might be beneficial for the treatment of diabetic nephropathy. The ability of LJE to attenuate proteinuria and podocyte dysfunction may be mediated by the inhibition of AGE accumulation in the context of diabetic nephropathy in db/db mice.

  13. Irbesartan treatment does not influence plasma levels of the advanced glycation end products N(epsilon)(1-carboxymethyl)lysine and N(epsilon)(1-carboxyethyl)lysine in patients with type 2 diabetes and microalbuminuria. A randomized controlled trial

    DEFF Research Database (Denmark)

    Engelen, Lian; Persson, Frederik; Ferreira, Isabel;

    2011-01-01

    BACKGROUND: In vitro and animal experiments have shown inhibiting effects of angiotensin receptor blockers (ARBs) on the formation of advanced glycation end products (AGEs), which are known to be involved in the development of cardiovascular complications in diabetes. However, sufficient human data...

  14. The Effect of Chang Run Tong on Biomechanical Colon Remodeling in STZ-Induced Type I Diabetic Rats - Is It Related to Advanced Glycation End Product Formation?

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Gregersen, Hans

    2015-01-01

    effects. Meterials and METHODS: Morphometric properties, residual strains and stress-strain of the wall were studied in colonic segments obtained from diabetic (DM), CRT treated diabetic (T1, high dosage: 50g/kg; T2, low dosage: 25g/kg) and normal (Con) rats. Diabetes was induced by a single tail vein...... and the opening angle were measured from the digitized images of the segments in the no-load state and zero-stress state. The residual strain was computed from the morphometry data. Step-wise distension was done (from 0 to 20 cmH2O). Circumferential and longitudinal stresses and strains were computed from...... the length, diameter and pressure data and from the zero-stress state geometry. The expression of advanced glycation end products (AGE) and receptor of AGE (RAGE) were detected in different layers by using immunohistochemistry method and quantitatively analyzed by using imaging analysis software. Linear...

  15. Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training

    DEFF Research Database (Denmark)

    Mattiello-Sverzut, Ana Claudia; Petersen, Susanne G; Kjaer, Michael;

    2013-01-01

    The aim of this study was to investigate the effect of 12-week resistance training on morphological presence of collagen and RAGE (receptor for advanced glycation end products) in skeletal muscle of patients with knee osteoarthritis (OA). Little is known about the influence of exercise...... on the skeletal muscle matrix that supports joints affected by OA mainly when it is associated with medication taken by OA patients (non-steroid anti-inflammatory drugs (NSAID) and glucosamine). A biopsy was collected from the vastus lateralis muscle in all patients before and after 12-week period of training....... The patients (age 55-69 years) were divided into three groups, treated with NSAID, glucosamine or placebo. In addition, the muscle samples were analysed by immunohistochemistry for collagen types, RAGE and capillaries ratio. An increment in immunoreactivity for type IV collagen after the training period...

  16. Systemic stiffening of mouse tail tendon is related to dietary advanced glycation end products but not high-fat diet or cholesterol

    DEFF Research Database (Denmark)

    Eriksen, Christian; Svensson, R B; Scheijen, J;

    2014-01-01

    ) cross-linking of non-weight-bearing mouse tail tendons. Twenty ApoE(-/-) male mice were used as a model for hypercholesterolemia along with 26 wild-type (WT) mice. One-half of the mice from each group was fed a normal diet (ND) and the other half was fed a high-fat diet (HFD) to induce obesity. All were......Tendon pathology is related to metabolic disease and mechanical overloading, but the effect of metabolic disease on tendon mechanics is unknown. This study investigated the effect of diet and apolipoprotein E deficiency (ApoE(-/-)) on mechanical properties and advanced glycation end product (AGE...... killed at 40 wk, and tail tendon fascicles were mechanically tested to failure and analyzed for AGEs. Diets were also analyzed for AGEs. ApoE(-/-) mice displayed a 14% increase in plateau modulus compared with WT mice (P

  17. Inhibition of Advanced Glycation End Products (AGEs Accumulation by Pyridoxamine Modulates Glomerular and Mesangial Cell Estrogen Receptor α Expression in Aged Female Mice.

    Directory of Open Access Journals (Sweden)

    Simone Pereira-Simon

    Full Text Available Age-related increases in oxidant stress (OS play a role in regulation of estrogen receptor (ER expression in the kidneys. In this study, we establish that in vivo 17β-estradiol (E2 replacement can no longer upregulate glomerular ER expression by 21 months of age in female mice (anestrous. We hypothesized that advanced glycation end product (AGE accumulation, an important source of oxidant stress, contributes to these glomerular ER expression alterations. We treated 19-month old ovariectomized female mice with pyridoxamine (Pyr, a potent AGE inhibitor, in the presence or absence of E2 replacement. Glomerular ERα mRNA expression was upregulated in mice treated with both Pyr and E2 replacement and TGFβ mRNA expression decreased compared to controls. Histological sections of kidneys demonstrated decreased type IV collagen deposition in mice receiving Pyr and E2 compared to placebo control mice. In addition, anti-AGE defenses Sirtuin1 (SIRT1 and advanced glycation receptor 1 (AGER1 were also upregulated in glomeruli following treatment with Pyr and E2. Mesangial cells isolated from all groups of mice demonstrated similar ERα, SIRT1, and AGER1 expression changes to those of whole glomeruli. To demonstrate that AGE accumulation contributes to the observed age-related changes in the glomeruli of aged female mice, we treated mesangial cells from young female mice with AGE-BSA and found similar downregulation of ERα, SIRT1, and AGER1 expression. These results suggest that inhibition of intracellular AGE accumulation with pyridoxamine may protect glomeruli against age-related oxidant stress by preventing an increase of TGFβ production and by regulation of the estrogen receptor.

  18. Research Progress of Preeclampsia and Advanced Glycation End Products%晚期糖基化终产物与子痫前期的研究进展

    Institute of Scientific and Technical Information of China (English)

    蒋玲玲

    2013-01-01

    Advanced glycation end products(AGEs) are formed by non-enzymatic reactions between carbonyl groups of reducing sugars and free amino groups of macromolecules such as proteins,lipoproteins and nucleic acids.AGEs can directly lead to cell damage,but also can play a biological effect by binding to the receptor.Studies have shown that AGEs had a closely relationship with mitochondrial oxidative stress damage and lipid metabolism disorders.Pre-eclampsia,a hypertensive disorder which occurs only during pregnancy,is a major cause of maternal-fetal morbidity and mortality.However,the mechanisms responsible for the pathogenesis of pre-eclampsia are not completely understood.It is generally agreed that mitochondrial oxidative stress damage and lipid metabolism disorders are involved in the pathogenesis of preeclampsia.This article reviews the role of AGEs in preeclampsia.%晚期糖基化终产物(advanced glycation end products,AGEs)是指蛋白质、核酸、脂质等大分子物质的氨基在无酶条件下生成的一组稳定的终末产物,既可直接损伤细胞,也能通过与受体结合发挥生物学效应.研究发现,AGEs与线粒体氧化应激损伤及脂质代谢紊乱关系密切.子痫前期是妊娠期特有的疾病,是孕产妇和围生儿患病及死亡的主要原因,但具体发病机制未明,现普遍认为线粒体氧化应激损伤及脂质代谢紊乱参与子痫前期发病.就AGEs在子痫前期发病中的作用进行综述.

  19. Inhibition of glucose- and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

    Directory of Open Access Journals (Sweden)

    Jugjeet Singh Ramkissoon

    2016-06-01

    Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation end-products-mediated complications.

  20. Characterization and cytological effects of a novel glycated gelatine substrate

    International Nuclear Information System (INIS)

    Hyperglycemia in diabetes results in the glycation of long-lived proteins. Protein glycation leads to the formation of advanced glycation end products (AGEs), which are implicated in delayed wound healing and other diabetes-associated pathologies, one of which is periodontal disease. Research into the mechanisms by which glycated long-lived proteins such as collagen exert their effects can allow for the understanding of diabetic pathologies and the development of appropriate treatments. However, the high cost of purified protein can be a limitation for many laboratories around the world. The objective of this study was to develop a low-cost in vitro model of glycated gelatine as an alternative to the glycated collagen model. We investigated the glycation of gelatine type A, a denatured form of collagen, which is low-cost and abundantly available. In this study, gelatine was incubated for 7 days with ribose or methylglyoxal (MG). Cross-linking, autofluorescence and UV–Vis spectrophotometry assays were performed and indicated a dose-dependent linear increase in cross-linking and autofluorescence of gelatine by ribose and MG. MG produced more cross-linking compared to ribose at the same concentrations. The UV–Vis spectra of the glycated gelatines confirmed the presence of AGE fluorophores. Because diabetes is a risk factor for periodontal disease, the effect of the glycated substrates on the basic behaviour of human periodontal ligament (HPDL) cells was evaluated. Glycation dose dependently reduced HPDL attachment and cell spreading, indicating that the novel glycated gelatine substrate affects cell behaviour. These results show that gelatine glycated with ribose or MG can be used as low-cost in vitro models to study the effects of protein glycation on cell behaviour in diabetes and ageing. (paper)

  1. Beneficial Effect of Traditional Chinese Medicinal Formula Danggui-Shaoyao-San on Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Diabetic Rats

    Directory of Open Access Journals (Sweden)

    I-Min Liu

    2012-01-01

    Full Text Available The present study was undertaken to characterize the effects of Danggui-Shaoyao-San (DSS, a famous traditional Chinese medicine formula consisting of six herbal medicines, on diabetic nephropathy. Streptozotocin-induced diabetic rats were orally administrated DSS (2.8 g kg−1 per day for 12 consecutive weeks. DSS partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-hour urinary albumin excretion rate, and creatinine clearance as well as the kidney hypertrophy (kidney weight/body weight ratio and glomerular mesangial matrix expansion were ameliorated after 12 weeks of DSS treatment. The increased expression of nuclear factor-κB as well as transforming growth factor-β1 and the progressive accumulation of type IV collagen in kidney of diabetic rats were also attenuated by DSS. Not only the elevated levels of advanced glycation end products (AGEs and Nε-(carboxymethyllysine but also the higher levels of lipid peroxidation products in kidney of diabetic rats were ameliorated by DSS. Decreased activity of superoxide diamutase and glutathione peroxidase in kidney of diabetic rats was enhanced by DSS. These data demonstrated that the renoprotective effects of DSS in STZ-diabetic rats not only were attributable to regulate plasma glucose to attenuate AGEs expression in diabetic glomeruli but also likely reflected its antioxidant activity.

  2. Advanced Glycation End Products Induce Endothelial-to-Mesenchymal Transition via Downregulating Sirt 1 and Upregulating TGF-β in Human Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Wei He

    2015-01-01

    Full Text Available In the present study, we examined the advanced glycation end products- (AGEs- induced endothelial-to-mesenchymal transition (EndMT in human umbilical vein endothelial cells (HUVECs. Results demonstrated that AGE-BSAs significantly reduced the cluster of differentiation 31 (CD 31 expression, whereas they promoted the expression of fibroblast-specific protein-1 (FSP-1, α-smooth muscle antibody (α-SMA, and collagen I at both mRNA and protein levels in HUVECs. And the AGE-BSAs also promoted the receptors for AGEs (RAGEs and receptor I for TGF-β (TGFR I markedly with a dose dependence, whereas the Sirt 1 was significantly downregulated by the AGE-BSA at both mRNA and protein levels. Moreover, the Sirt 1 activity manipulation with its activator, resveratrol (RSV, or its inhibitor, EX527, markedly inhibited or ameliorated the AGE-mediated TGF-β upregulation. And the manipulated Sirt 1 activity positively regulated the AGE-induced CD31, whereas it negatively regulated the AGE-induced FSP-1. Thus, Sirt 1 was confirmed to regulate the AGE-induced EndMT via TGF-β. In summary, we found that AGE-BSA induced EndMT in HUVECs via upregulating TGF-β and downregulating Sirt 1, which also negatively regulated TGF-β in the cell. This study implied the EndMT probably as an important mechanism of AGE-induced cardiovascular injury.

  3. Advanced Glycation End Products (AGE) Potently Induce Autophagy through Activation of RAF Protein Kinase and Nuclear Factor κB (NF-κB).

    Science.gov (United States)

    Verma, Neeharika; Manna, Sunil K

    2016-01-15

    Advanced glycation end products (AGE) accumulate in diabetic patients and aging people because of high amounts of three- or four-carbon sugars derived from glucose, thereby causing multiple consequences, including inflammation, apoptosis, obesity, and age-related disorders. It is important to understand the mechanism of AGE-mediated signaling leading to the activation of autophagy (self-eating) that might result in obesity. We detected AGE as one of the potent inducers of autophagy compared with doxorubicin and TNF. AGE-mediated autophagy is inhibited by suppression of PI3K and potentiated by the autophagosome maturation blocker bafilomycin. It increases autophagy in different cell types, and that correlates with the expression of its receptor, receptor for AGE. LC3B, the marker for autophagosomes, is shown to increase upon AGE stimulation. AGE-mediated autophagy is partially suppressed by inhibitor of NF-κB, PKC, or ERK alone and significantly in combination. AGE increases sterol regulatory element binding protein activity, which leads to an increase in lipogenesis. Although AGE-mediated lipogenesis is affected by autophagy inhibitors, AGE-mediated autophagy is not influenced by lipogenesis inhibitors, suggesting that the turnover of lipid droplets overcomes the autophagic clearance. For the first time, we provide data showing that AGE induces several cell signaling cascades, like NF-κB, PKC, ERK, and MAPK, that are involved in autophagy and simultaneously help with the accumulation of lipid droplets that are not cleared effectively by autophagy, therefore causing obesity.

  4. Phenolic acids inhibit the formation of advanced glycation end products in food simulation systems depending on their reducing powers and structures.

    Science.gov (United States)

    Chen, Hengye; Virk, Muhammad Safiullah; Chen, Fusheng

    2016-06-01

    The concentration of advanced glycation end products (AGEs) in foods, which are formed by Maillard reaction, has demonstrated as risk factors associated with many chronic diseases. The AGEs inhibitory activities of five common phenolic acids (protocatechuic acid, dihydroferulic acid, p-coumaric acid, p-hydroxybenzoic acid and salicylic acid) with different chemical properties had been investigated in two food simulation systems (glucose-bovine serum albumin (BSA) and oleic acid-BSA). The results substantiated that the AGEs inhibitory abilities of phenolic acids in the oleic acid BSA system were much better than the glucose-BSA system for their strong reducing powers and structures. Among them, dihydrogenferulic acid showed strong inhibition of AGEs formation in oleic acid-BSA system at 0.01 mg/mL compared to nonsignificant AGEs inhibitory effect in oleic acid-BSA system at 10-fold higher concentration (0.1 mg/mL). This study suggests that edible plants rich in phenolic acids may be used as AGEs inhibitor during high-fat cooking. PMID:27102241

  5. Advanced glycation end product-induced astrocytic differentiation of cultured neurospheres through inhibition of Notch-Hes1 pathway-mediated neurogenesis.

    Science.gov (United States)

    Guo, Yijing; Wang, Pin; Sun, Haixia; Cai, Rongrong; Xia, Wenqing; Wang, Shaohua

    2014-01-01

    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 culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits.

  6. Receptor for advanced glycation end products plays a more important role in cellular survival than in neurite outgrowth during retinoic acid-induced differentiation of neuroblastoma cells.

    Science.gov (United States)

    Sajithlal, Gangadharan; Huttunen, Henri; Rauvala, Heikki; Munch, Gerald

    2002-03-01

    The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, is known to interact with amphoterin. This interaction has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, there is as yet no direct evidence of the relevance of this pathway to neurodifferentiation under physiological conditions. In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of RAGE by dominant negative and antisense strategies showed that RAGE is not required for process outgrowth or differentiation, although overexpression of RAGE accelerates the elongation of neuritic processes. Using the antisense strategy, amphoterin was shown to be essential for process outgrowth and differentiation, suggesting that amphoterin may interact with other molecules to exert its effect in this context. Interestingly, the survival of the neuroblastoma cells treated with retinoic acid was partly dependent on the expression of RAGE, and inhibition of RAGE function partially blocked the increase in anti-apoptotic protein Bcl-2 following retinoic acid treatment. Based on these results we propose that a combination therapy using RAGE blockers and retinoic acid may prove as a useful approach for chemotherapy for the treatment of neuroblastoma.

  7. Voltammetric Detection of S100B Protein Using His-Tagged Receptor Domains for Advanced Glycation End Products (RAGE Immobilized onto a Gold Electrode Surface

    Directory of Open Access Journals (Sweden)

    Edyta Mikuła

    2014-06-01

    Full Text Available In this work we report on an electrochemical biosensor for the determination of the S100B protein. The His-tagged VC1 domains of Receptors for Advanced Glycation End (RAGE products used as analytically active molecules were covalently immobilized on a monolayer of a thiol derivative of pentetic acid (DPTA complex with Cu(II deposited on a gold electrode surface. The recognition processes between the RAGE VC1 domain and the S100B protein results in changes in the redox activity of the DPTA-Cu(II centres which were measured by Osteryoung square-wave voltammetry (OSWV. In order to verify whether the observed analytical signal originates from the recognition process between the His6–RAGE VC1 domains and the S100B protein, the electrode modified with the His6–RAGE C2 and His6–RAGE VC1 deleted domains which have no ability to bind S100B peptides were applied. The proposed biosensor was quite sensitive, with a detection limit of 0.52 pM recorded in the buffer solution. The presence of diluted human plasma and 10 nM Aβ1-40 have no influence on the biosensor performance.

  8. Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.

    Science.gov (United States)

    Zhang, Ting; Hu, Xiaorong; Cai, Yuli; Yi, Bo; Wen, Zhongyuan

    2014-03-01

    Metformin (MET), an anti-diabetic oral drug with antioxidant properties, has been proved to provide cardioprotective effects in patients with diabetic disease. However, the mechanism is unclear. This study aimd to investigate the effects of MET on the expressions of receptor for advanced glycation end products (RAGE) and high mobility group box 1 protein (HMGB1) in hyperglycemia-treated neonatal rat ventricular myocytes. Cardiocytes were prepared and cultured with high glucose and different concentrations of MET. The expressions of RAGE and HMGB1 were evaluated by Western blot analysis. The superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured. After 12 h-incubation, MET significantly inhibited the increase of MDA, TNF-α, LDH and CK levels induced by high glucose, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations while inhibiting the decrease of SOD level. Meanwhile, RAGE and HMGB1 expression were significantly increased induced by hyperglycaemia for 24 h (P < 0.05). MET inhibited the expressions of RAGE and HMGB1 in a dose-dependent manner, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations (P < 0.05). In conclusion, our study suggested that MET could reduce hyperglycemia-induced cardiocytes injury by inhibiting the expressions of RAGE and HMGB1. PMID:24420848

  9. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

  10. The Effect of a Phaseolus vulgaris and Dietary Fiber Based Supplement on Advanced Glycation End Products: An Open-label Trial

    Directory of Open Access Journals (Sweden)

    Brett J. West

    2015-07-01

    Full Text Available Elevated Advanced Glycation End product (AGE levels are associated with certain impaired health states. As these are disruptive to the function of healthy tissues, due to their protein cross-linking ability, AGEs are significant contributors to the aging process. In fact, population studies have revealed that AGE levels tend to increase as we get older. Certain lifestyle and dietary factors may accelerate AGE accumulation. Therefore, strategies intended to modify these factors, or mitigate their effects, may be useful in controlling the aging process. In an 11 week open-label clinical trial, 30 adult volunteers consumed daily a commercially available combination of white kidney bean extract, dietary fibers, &beta-carotene and noni (Morinda citrifolia fruit pulp, in combination with calorie restriction and exercise. During the course of the trial, participants experienced significant weekly declines in average body weight and fat mass. The average AGE score, as measured by skin auto-fluorescence, had also decreased significantly. In terms of AGE associated years, the change in AGE scores corresponded to an average decrease of 8.83 years. The results indicate that the intervention contributed to improved health and exhibited anti-aging properties.

  11. Cells and Tissue Interactions with Glycated Collagen and their Relevance to Delayed Diabetic Wound Healing

    OpenAIRE

    LIAO, HUIJUAN; Zakhaleva, Julia; Chen, Weiliam

    2009-01-01

    Dermal accumulation of advanced glycation end products (AGEs) has increasingly been implicated as the underlying cause of delayed diabetic wound healing. Devising an in vitro model to adequately mimic glycated tissues will facilitate investigation into the mechanism of glycation in conjunction with exploration of new approaches or improvement of current therapies for treating diabetic chronic wounds. Collagen matrices were artificially glycated and the presence of AGEs was demonstrated by imm...

  12. The effects of Advanced Glycation End Products (RAGE)-374T/A and Gly82Ser variants and soluble-RAGE levels to obesity in children.

    Science.gov (United States)

    Kucukhuseyin, O; Ozgen, T; Karagedik, E H; Cesur, Y; Yilmaz Aydogan, H; Yaylim, I; Ergen, H A

    2016-04-30

    In recent years, studies related to advanced glycation end products (AGE) and their interaction with their receptors (RAGE) have advanced our knowledge of the roles of these molecules in different diseases. However, studies concerning AGE-RAGE interaction in obesity are limited and the results are conflicting. RAGE gene is located on 6p21.3, has several polymorphic sites including -374T/A, a functional polymorphism in the promoter region, and Gly82Ser, present within the ligand-binding domain. In the present study, the determination of possible risks in the development of obesity according to RAGE polymorhisms and plasma levels of RAGE (sRAGE) was aimed. 87 obese and 78 healthy children were included in this study. Genomic DNA was isolated with salting-out procedure. RAGE polymorphisms were analyzed by PCR based techniques. In contrast to Gly82Ser, -374T/A allelic and genotypic frequencies were not different between study groups. Ser(SerSer+GlySer genotype) allele frequency was higher in obese cases than controls (74.20%→25.80%,OR:2.573,95%CI:1.789-3.699;pGlySer>GlyGly for HDL-C, and opposite for FT4. Besides, Ser carriers had lower insulin (p=0.038) and homa-IR (p=0.081) levels than GG genotype. sRAGE levels were different between obese and control seperately or in combination with RAGE polymorphisms (pTA>AA for -374T/A and SerSer>GlyGly>GlySer for Gly82Ser. According to our results SerSer genotype could have significant effects on sRAGE levels, and increased sRAGE levels and Gly82Ser polymorphism either combinatorially or seperately increased the propensity towards obesity.

  13. 晚期糖基化终末产物与糖尿病性骨质疏松%Advanced glycation end products and diabetic osteoporosis

    Institute of Scientific and Technical Information of China (English)

    杨力; 程彦臻; 蔡德鸿

    2012-01-01

    晚期糖基化终末产物(AGEs)是由蛋白质经非酶催化的Maillard反应所形成,糖尿病时AGEs的形成和积累加速.AGEs与其受体(RAGE)结合后,引起氧化应激及炎性反应,继而导致成骨细胞、破骨细胞及骨髓间充质干细胞功能改变;同时AGEs与骨基质中胶原蛋白交联还可使骨强度下降,是造成糖尿病性骨质疏松的主要原因.检测血清及尿液中的AGEs成分,可作为评估糖尿病患者骨折发生风险的有效指标.%Advanced glycation end products (AGEs) are chemical modifications of proteins by nonenzymatic Maillard reaction.The formation and accumulation of AGEs have been known to be accelerated when suffered from diabetes.Combinations of AGEs and their receptors (RAGE) cause oxidative stress and inflammation,which result in functional alterations of osteoblasts,osteoclasts and bone mesenchymal stem cells.On the other hand,overcrossslinking of AGEs and collagen can also cause loss of flexibility and elasticity and increase brittleness of bone.Accordingly,AGEs play an crucial role in the development of diabetic osteoporosis.Measurement of serum and urinary AGEs composition can be effective for predicting diabetic osteoporosis.

  14. High-mobility group box 1 inhibits gastric ulcer healing through Toll-like receptor 4 and receptor for advanced glycation end products.

    Science.gov (United States)

    Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Ohkawa, Fumikazu; Takeda, Shogo; Higashimori, Akira; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Takeuchi, Koji; Arakawa, Tetsuo

    2013-01-01

    High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR) 2, TLR4, and receptor for advanced glycation end products (RAGE), leading to tissue injury. Although HMGB1's ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1's effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO) activity, and the expression of tumor necrosis factor α (TNFα) mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO) mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses.

  15. Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation.

    Science.gov (United States)

    Huang, Yen-Kai; Chou, Ruey-Hwang; Yu, Chin

    2016-07-01

    The human S100 calcium-binding protein A11 (S100A11) is a member of the S100 protein family. Once S100A11 proteins bind to calcium ions at EF-hand motifs, S100A11 changes its conformation, promoting interaction with target proteins. The receptor for advanced glycation end products (RAGE) consists of three extracellular domains, including the V domain, C1 domain, and C2 domain. In this case, the V domain is the target for mutant S100A11 (mS100A11) binding. RAGE binds to the ligands, resulting in cell proliferation, cell growth, and several signal transduction cascades. We used NMR and fluorescence spectroscopy to demonstrate the interactions between mS100A11and RAGE V domain. The tranilast molecule is a drug used for treating allergic disorders. We discovered that the RAGE V domain and tranilast would interact with mS100A11 by using (1)H-(15)N HSQC NMR titrations. According to the results, we obtained two binary complex models from the HADDOCK program, S100A11-RAGE V domain and S100A11-tranilast, respectively. We overlapped two binary complex models with the same orientation of S100A11 homodimer and demonstrated that tranilast would block the binding site between S100A11 and the RAGE V domain. We further utilized a water-soluble tetrazolium-1 assay to confirm this result. We think that the results will be potentially useful in the development of new anti-cancer drugs. PMID:27226584

  16. An improved expression system for the VC1 ligand binding domain of the receptor for advanced glycation end products in Pichia pastoris.

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    Degani, Genny; Colzani, Mara; Tettamanzi, Alberto; Sorrentino, Luca; Aliverti, Alessandro; Fritz, Guenter; Aldini, Giancarlo; Popolo, Laura

    2015-10-01

    The receptor for the advanced glycation end products (RAGE) is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily and binds a variety of unrelated ligands sharing a negative charge. Most ligands bind to the extracellular V or VC1 domains of the receptor. In this work, V and VC1 of human RAGE were produced in the methylotrophic yeast Pichia pastoris and directed to the secretory pathway. Fusions to a removable C-terminal His-tag evidenced proteolytic processing of the tag by extracellular proteases and also intracellular degradation of the N-terminal portion of V-His. Expression of untagged forms was attempted. While the V domain was retained intracellularly, VC1 was secreted into the medium and was functionally active in binding AGEs. The glycosylation state of VC1 was analyzed by mass spectrometry and peptide-N-glycosidase F digestion. Like RAGE isolated from mammalian sources, the degree of occupancy of the N-glycosylation sites was full at Asn25 and partial at Asn81 which was also subjected to non-enzymatic deamidation. A simple procedure for the purification to homogeneity of VC1 from the medium was developed. The folded state of the purified protein was assessed by thermal shift assays. Recombinant VC1 from P. pastoris showed a remarkably high thermal stability as compared to the protein expressed in bacteria. Our in vivo approach indicates that the V and C1 domains constitute a single folding unit. The stability and solubility of the yeast-secreted VC1 may be beneficial for future in vitro studies aimed to identify new ligands or inhibitors of RAGE. PMID:26118699

  17. High-mobility group box 1 inhibits gastric ulcer healing through Toll-like receptor 4 and receptor for advanced glycation end products.

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    Yuji Nadatani

    Full Text Available High-mobility group box 1 (HMGB1 was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR 2, TLR4, and receptor for advanced glycation end products (RAGE, leading to tissue injury. Although HMGB1's ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1's effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO activity, and the expression of tumor necrosis factor α (TNFα mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses.

  18. Aliskiren attenuates bleomycin-induced pulmonary fibrosis in rats: focus on oxidative stress, advanced glycation end products, and matrix metalloproteinase-9.

    Science.gov (United States)

    Abuelezz, Sally A; Hendawy, Nevien; Osman, Wesam M

    2016-08-01

    Pulmonary fibrosis is a progressive lung disorder with high mortality rate and limited successful treatment. This study was designed to assess the potential anti-oxidant and anti-fibrotic effects of aliskiren (Alsk) during bleomycin (BLM)-induced pulmonary fibrosis. Male Wistar rats were used as control untreated or treated with the following: a single dose of 2.5 mg/kg of BLM endotracheally and BLM and Alsk (either low dose 30 mg/kg/day or high dose 60 mg/kg/day), and another group was given Alsk 60 mg/kg/day alone. Alsk was given by gavage. Alsk anti-oxidant and anti-fibrotic effects were assessed. BLM significantly increased relative lung weight and the levels of lactate dehydrogenase and total and differential leucocytic count in bronchoalveolar lavage that was significantly ameliorated by high-dose Alsk treatment. As markers of oxidative stress, BLM caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease of superoxide dismutase and glutathione transferase enzymes. High-dose Alsk treatment restored these markers toward normal values. Alsk counteracted the overexpression of advanced glycation end products, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 in lung tissue induced by BLM. Fibrosis assessed by measuring hydroxyproline content, which markedly increased in the BLM group, was also significantly reduced by Alsk. These were confirmed by histopathological and immunohistochemical examination which revealed that Alsk attenuates signs of pulmonary fibrosis and decreased the overexpressed MMP-9 and transforming growth factor β1. Collectively, these findings indicate that Alsk has a potential anti-fibrotic effect beside its anti-oxidant activity. PMID:27154762

  19. Involvement of formyl peptide receptors in receptor for advanced glycation end products (RAGE - and amyloid beta 1-42-induced signal transduction in glial cells

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    Slowik Alexander

    2012-11-01

    Full Text Available Abstract Background Recent studies suggest that the chemotactic G-protein-coupled-receptor (GPCR formyl-peptide-receptor-like-1 (FPRL1 and the receptor-for-advanced-glycation-end-products (RAGE play an important role in the inflammatory response involved in neurodegenerative disorders such as Alzheimer’s disease (AD. Therefore, the expression and co-localisation of mouse formyl peptide receptor (mFPR 1 and 2 as well as RAGE in an APP/PS1 transgenic mouse model using immunofluorescence and real-time RT-PCR were analysed. The involvement of rat or human FPR1/FPRL1 (corresponds to mFPR1/2 and RAGE in amyloid-β 1–42 (Aβ1-42-induced signalling were investigated by extracellular signal regulated kinase 1/2 (ERK1/2 phosphorylation. Furthermore, the cAMP level in primary rat glial cells (microglia and astrocytes and transfected HEK 293 cells was measured. Formyl peptide receptors and RAGE were inhibited by a small synthetic antagonist WRW4 and an inactive receptor variant delta-RAGE, lacking the intracytoplasmatic domains. Results We demonstrated a strong increase of mFPR1/2 and RAGE expression in the cortex and hippocampus of APP/PS1 transgenic mice co-localised to the glial cells. In addition, the Aβ1-42-induced signal transduction is dependant on FPRL1, but also on FPR1. For the first time, we have shown a functional interaction between FPRL1/FPR1 and RAGE in RAGE ligands S100B- or AGE-mediated signalling by ERK1/2 phosphorylation and cAMP level measurement. In addition a possible physical interaction between FPRL1 as well as FPR1 and RAGE was shown with co-immunoprecipitation and fluorescence microscopy. Conclusions The results suggest that both formyl peptide receptors play an essential role in Aβ1-42-induced signal transduction in glial cells. The interaction with RAGE could explain the broad ligand spectrum of formyl peptide receptors and their important role for inflammation and the host defence against infections.

  20. Advanced glycation end products promote human aortic smooth muscle cell calcification in vitro via activating NF-κB and down-regulating IGF1R expression

    Institute of Scientific and Technical Information of China (English)

    Yi WANG; Zhen-yu ZHANG; Xiao-qing CHEN; Xiang WANG; Heng CAO; Shao-wen LIU

    2013-01-01

    Aim:To investigate the effects of advanced glycation end products (AGEs) on calcification in human aortic smooth muscle cells (HASMCs) in vitro and the underlying mechanisms.Methods:AGEs were artificially prepared.Calcification of HASMCs was induced by adding inorganic phosphate (Pi,2 mmol/L) in the media,and observed with Alizarin red staining.The calcium content in the supernatant was measured using QuantiChrome Calcium Assay Kit.Expression of the related mRNAs and proteins was analyzed using real-time PCR and Western blot,respectively.Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NF-κB to the putative IGF1R promoter.Results:AGEs (100 μg/mL) significantly enhanced Pi-induced calcification and the levels of osteocalcin and Cbfα1 in HASMCs.Furthermore,the treatment decreased the expression of insulin-like growth factor 1 receptor (IGF1R).Over-expression of IGF1R in HASMCs suppressed the AGEs-induced increase in calcium deposition.When IGF1R expression was knocked down in HASMCs,AGEs did not enhance the calcium deposition.Meanwhile,AGEs time-dependently decreased the amounts of IκBα and Flag-tagged p65 in the cytoplasmic extracts,and increased the amount of nuclear p65 in HASMCs.In the presence of NF-κB inhibitor PDTC (50 μmol/L),the AGEs-induced increase in calcium deposition was blocked.Over-expression of p65 significantly enhanced Pi-induced mineralization,but suppressed IGF1R mRNA level.Knockdown of p65 suppressed the AGEs-induced increase in calcium deposition,and rescued the IGF1R expression.The ChIP analysis revealed that NF-κB bound the putative IGF1R promoter at position-230 to-219 bp.The inhibition of IGF1R by NF-κB was abolished when IGF1R reporter plasmid contained mutated binding sequence for NF-κB or an NF-κB reporter vector.Conclusion:The results demonstrate that AGEs promote calcification of human aortic smooth muscle cells in vitro via activation of NF-κB and down-regulation of IGF1R expression.

  1. High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.

    Science.gov (United States)

    Good, David W; George, Thampi; Watts, Bruns A

    2015-10-15

    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296-C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO(3)(-) absorption through the same pathway. Adding HMGB1 to the bath decreased HCO(3)(-) absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4(-/-) mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO(3)(-) absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO(3)(-) absorption mediated through Na⁺/H⁺ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO(3)(-) absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO(3)(-) absorption through

  2. HMGB1 Contributes to the Expression of P-Glycoprotein in Mouse Epileptic Brain through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products.

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    Yan Chen

    Full Text Available The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1 in the seizure-induced P-glycoprotein (P-gp overexpression and the underlying mechanism. Kainic acid (KA-induced mouse seizure model was used for in vivo experiments. Male C57BL/6 mice were divided into four groups: normal saline control (NS group, KA-induced epileptic seizure (EP group, and EP group pretreated with HMGB1 (EP+HMGB1 group or BoxA (HMGB1 antagonist, EP+BoxA group. Compared to the NS group, increased levels of HMGB1 and P-gp in the brain were observed in the EP group. Injection of HMGB1 before the induction of KA further increased the expression of P-gp while pre-treatment with BoxA abolished this up-regulation. Next, the regulatory role of HMGB1 and its potential involved signal pathways were investigated in mouse microvascular endothelial bEnd.3 cells in vitro. Cells were treated with HMGB1, HMGB1 plus lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS [toll-like receptor 4 (TLR4 antagonist], HMGB1 plus FPS-ZM1 [receptor for advanced glycation end products (RAGE inhibitor], HMGB1 plus SN50 [nuclear factor-kappa B (NF-κB inhibitor], or vehicle. Treatment with HMGB1 increased the expression levels of P-gp, TLR4, RAGE and the activation of NF-κB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-κB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene in endothelial cells. These data indicate that HMGB1 contributes to the overexpression of P-gp in mouse epileptic brain tissues via activation of TLR4/RAGE receptors and the downstream transcription factor NF-κB in brain microvascular endothelial cells.

  3. Concentration of Endogenous Secretory Receptor for Advanced Glycation End Products and Matrix Gla Protein in Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients

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    Dwi Yuniati Daulay

    2013-04-01

    Full Text Available BACKGROUND: Advanced glycation end products (AGE and their receptor (RAGE system play an important role in the development of diabetic vascular complications. Recently, an endogenous secretory RAGE (esRAGE has been identified as a novel splice variant, which lacks the transmembrane domain and is secreted in human sera. Interestingly, it was reported that esRAGE binds AGE ligands and neutralizes AGE actions. Many studies have reported that diabetes mellitus correlates with vascular calcification event and increases progressively in uncontrolled diabetes. Matrix Gla Protein (MGP is known to act as an inhibitor in vascular calcification. The aim of this study was to observe progress of vascular calcification in uncontrolled diabetes patient by biochemical markers MGP as inhibitor in vascular calcification, via mechanism of AGEs. METHODS: This study was an observational study with cross sectional design on adult type 2 diabetic male patients who were defined by the 2011 Indonesian diabetes mellitus consensus criteria. RESULTS: The results of this study showed that there was a positive significant correlation between esRAGE and HbA1C (r=0.651, p=0.009, and negative correlation between MGP and HbA1C (r=-0.465, p=0.081 in controlled diabetes group. In uncontrolled diabetes group there was a positive significant correlation between MGP and HbA1C (r=0.350, p=0.023, despite the fact esRAGE showed no significant correlation with HbA1C. There was no significant difference in level of esRAGE and MGP in controlled and uncontrolled diabetes group, but MGP showed lower level in uncontrolled diabetes group, contrary to esRAGE that had higher concentration. CONCLUSIONS: In diabetes condition, complications of vascular calcification are caused by the mechanism of increased AGE formation represented by esRAGE. In diabetes control it is very important to keep the blood vessels from complications caused by vascular calcification. KEYWORDS: type 2 diabetes mellitus

  4. Glycation of the muscle-specific enolase by reactive carbonyls: effect of temperature and the protection role of carnosine, pyridoxamine and phosphatidylserine.

    Science.gov (United States)

    Pietkiewicz, Jadwiga; Bronowicka-Szydełko, Agnieszka; Dzierzba, Katarzyna; Danielewicz, Regina; Gamian, Andrzej

    2011-03-01

    Reactive carbonyls such as 4-hydroxy-2-nonenal (4-HNE), trans-2-nonenal (T2 N), acrolein (ACR) can react readily with nucleophilic protein sites forming of advanced glycation end-products (AGE). In this study, the human and pig muscle-specific enolase was used as a protein model for in vitro modification by 4-HNE, T2 N and ACR. While the human enolase interaction with reactive α-oxoaldehyde methylglyoxal (MOG) was demonstrated previously, the effect of 4-HNE, T2N and ACR has not been identified yet. Altering in catalytic function were observed after the enzyme incubation with these active compounds for 1-24 h at 25, 37 and 45 °C. The inhibition degree of enolase activity occurred in following order: 4-HNE > ACR > MOG > T2N and inactivation of pig muscle-specific enolase was more effective relatively to human enzyme. The efficiency of AGE formation depends on time and incubation temperature with glycating agent. More amounts of insoluble AGE were formed at 45 °C. We found that pyridoxamine and natural dipeptide carnosine counteracted AGE formation and protected enolase against the total loss of catalytic activity. Moreover, we demonstrated for the first time that phosphatidylserine may significantly protect enolase against decrease of catalytic activity in spite of AGE production. PMID:21347838

  5. Inhibitory effect of different fennel (Foeniculum vulgare) samples and their phenolic compounds on formation of advanced glycation products and comparison of antimicrobial and antioxidant activities.

    Science.gov (United States)

    Salami, Maryam; Rahimmalek, Mehdi; Ehtemam, Mohammad Hossein

    2016-12-15

    In this study, antioxidant, antibacterial and antiglycation properties of methanolic extracts of 23 fennel samples were evaluated and their major compounds were determined using HPLC analysis. The anti-glycative activity of extracts was evaluated in the bovine serum albumin (BSA)/glucose system. The level of glycation, conformational alterations and protein binding to RAGE receptors were assessed by Congo red binding assay and a brown staining method. Among samples, Kh1 from Iran possessed the highest TFC (14.8mgQUEg(-1)), TPC (262mg/g DW) and antioxidant activity (IC50=76μg/ml). The HPLC results revealed high variation in 23 fennel samples according to their major flavonoid (quercetin, apigenin and rutin) and phenolic (chlorogenic, caffeic and 1,5-dicaffeoylquinic acid) compounds. The antibacterial activity of methanolic extracts against four food-borne pathogens was also assessed. The seed extracts of Kh1 and En samples showed moderate to good inhibitory activities (MICs=62.5-125μg/ml) against three bacteria, as well as high anti-glycative activity. PMID:27451172

  6. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    Science.gov (United States)

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation. PMID:26893056

  7. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    Science.gov (United States)

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation.

  8. Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway.

    Science.gov (United States)

    Meng, Hong-Zheng; Zhang, Wei-Lin; Liu, Fei; Yang, Mao-Wei

    2015-11-20

    The interaction between advanced glycation end products (AGEs) and receptor of AGEs (RAGE) is associated with the development and progression of diabetes-associated osteoporosis, but the mechanisms involved are still poorly understood. In this study, we found that AGE-modified bovine serum albumin (AGE-BSA) induced a biphasic effect on the viability of hFOB1.19 cells; cell proliferation was stimulated after exposure to low dose AGE-BSA, but cell apoptosis was stimulated after exposure to high dose AGE-BSA. The low dose AGE-BSA facilitates proliferation of hFOB1.19 cells by concomitantly promoting autophagy, RAGE production, and the Raf/MEK/ERK signaling pathway activation. Furthermore, we investigated the effects of AGE-BSA on the function of hFOB1.19 cells. Interestingly, the results suggest that the short term effects of low dose AGE-BSA increase osteogenic function and decrease osteoclastogenic function, which are likely mediated by autophagy and the RAGE/Raf/MEK/ERK signal pathway. In contrast, with increased treatment time, the opposite effects were observed. Collectively, AGE-BSA had a biphasic effect on the viability of hFOB1.19 cells in vitro, which was determined by the concentration of AGE-BSA and treatment time. A low concentration of AGE-BSA activated the Raf/MEK/ERK signal pathway through the interaction with RAGE, induced autophagy, and regulated the proliferation and function of hFOB1.19 cells.

  9. Non-enzymatic Glycation of Almond Cystatin Leads to Conformational Changes and Altered Activity.

    Science.gov (United States)

    Siddiqui, Azad A; Sohail, Aamir; Bhat, Sheraz A; Rehman, Md T; Bano, Bilqees

    2015-01-01

    The non-enzymatic reaction between proteins and reducing sugars, known as glycation, leads to the formation of inter and intramolecular cross-links of proteins. Stable end products called as advanced Maillard products or advanced glycation end products (AGEs) have received tremendous attention since last decades. It was suggested that the formation of AGEs not only modify the conformation of proteins but also induces altered biological activity. In this study, cystatin purified from almond was incubated with three different sugars namely D-ribose, fructose and lactose to monitor the glycation process. Structural changes induced in cystatin on glycation were studied using UV-visible spectroscopy, fluorescence spectroscopy, CD and FTIR techniques. Glycated cystatin was found to migrate slower on electrophoresis as compared to control cystatin. Biological activity data of glycated cystatin showed that D-ribose was most effective in inducing conformational changes with maximum altered activity.

  10. Plantamajoside Inhibits UVB and Advanced Glycation End Products-Induced MMP-1 Expression by Suppressing the MAPK and NF-κB Pathways in HaCaT Cells.

    Science.gov (United States)

    Han, Ah-Ram; Nam, Mi-Hyun; Lee, Kwang-Won

    2016-09-01

    Photoaging and glycation stress are major causes of skin deterioration. Oxidative stress caused by ultraviolet B (UVB) irradiation can upregulate matrix metalloprotease 1 (MMP-1), a major enzyme responsible for collagen damage in the skin. Advanced glycation end products (AGEs) accumulate via gradual formation from skin proteins, especially from long-lived proteins such as dermal elastin and collagen. Plantamajoside (PM), isolated from Plantago asiatica, has various biological effects including anti-inflammatory and antioxidant effects. In this study, we assessed the protective effects of PM on a human keratinocyte cell line (HaCaT) and primary human dermal fibroblasts (HDF) against stress caused by glyceraldehyde-induced AGEs (glycer-AGEs) with UVB irradiation. We found that PM attenuated UVB- and-glycer-AGEs-induced MMP-1 expression in HaCaT and HDF cells and proinflammatory cytokines expression by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) activated by reactive oxygen species. Specific inhibitors of NF-κB and MAPKs attenuated the induced expression of MMP-1. PM also inhibited the phosphorylation of IκBα, and reduced nuclear translocation of NF-κB in these cells. Furthermore, PM attenuated the upregulation of receptor for AGEs (RAGE) by glycer-AGEs with UVB irradiation. Therefore, our findings strongly suggest that PM is a promising inhibitor of skin photoaging. PMID:27346084

  11. Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE expression in human embryonic kidney cells

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    Jyh-Gang Leu

    Full Text Available The anti-oxidant effects of epigallocatechin gallate (EGCG and alpha lipoic acid (ALA have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG-induced TNF-α and IL-6 production in human embryonic kidney (HEK cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.Os efeitos antioxidantes de galato de epigalocatequina (EGCG e ácido alfa lipóico (ALA foram demonstrados em estudos anteriores. Os efeitos renais da proteção de EGCG e ALA em pacientes com lesão renal ainda estão sob investigação. A finalidade deste estudo é investigar os efeitos anti-inflamatórios e antioxidantes de EGCG e ALA em lesão de células de rim humano induzida pela alta glicose. EGCG inibiu a produção de TNF-α e IL-6 induzida por HG em células de rim embrionário humano (HEK. Ambos EGCG e ALA diminuíram o mRNA do receptor de produtos finais de glicação avançada (RAGE induzida por HG e a expressão de proteínas em células HEK. EGCG e ALA também recuperaram a produção de superóxido dismutase inibida por HG e diminuíram a expressão de ROS em células HEK. O sinergismo de EGCG e ALA também foi estudado. O efeito de EGCG combinado com ALA é maior do que o efeito de EGCG sozinho

  12. 糖基化终产物在糖尿病眼部并发症中的作用研究进展%Recent research on advanced glycation-end products in pathobiology of ocular complications of diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    王旭; 严宏

    2015-01-01

    糖基化终产物(advanced glycation-end products,AGEs)是在持续高糖状态下,蛋白质的氨基与糖的醛基在非酶催化反应下生成的终产物,与糖尿病慢性并发症的发生发展密切相关.AGEs可以导致多种眼部疾病发生,如糖尿病性白内障、糖尿病视网膜病变、黄斑病变及青光眼等.本文就AGEs的生成及其参与糖尿病相关眼病的可能作用机制进行综述.

  13. Silica-based cerium (III) chloride nanoparticles prevent the fructose-induced glycation of α-crystallin and H₂O₂-induced oxidative stress in human lens epithelial cells.

    Science.gov (United States)

    Yang, Jin; Cai, Lei; Zhang, Sen; Zhu, Xiangjia; Zhou, Peng; Lu, Yi

    2014-03-01

    This study aimed to investigate whether silica-cerium (III) chloride (CeCl3) nanoparticles could inhibit the formation of advanced glycation end-products (AGEs) and reduce oxidative stress. Silica-CeCl3 nanoparticles were synthesised by adsorption and embedment with micro-silica materials, forming uniform nanoparticles with a diameter of approximately 130 nm. Chaperone activity assays and AGEs formation assays, and intracellular reactive assays were adopted in this study to evaluate CeCl3 nanoparticles effect. UV-visible spectrometry showed that silica-CeCl3 nanoparticles at low concentrations rapidly formed tentatively stable conjugations with α-crystallin, greatly enhancing the chaperone activity of α-crystallin. Moreover, silica-CeCl3 nanoparticles markedly inhibited the fructose-induced glycation of α-crystallin, showing an advantage over the control drugs aminoguanidine and carnosine. Silica-CeCl3 nanoparticles also reduced intracellular reactive oxygen species production and restored glutathione levels in H2O2-treated human lens epithelial cells. These findings suggest that silica-CeCl3 may be used as a novel agent for the prevention of cataractogenesis. PMID:23828754

  14. Similarity of the yellow chromophores isolated from human cataracts with those from ascorbic acid-modified calf lens proteins: evidence for ascorbic acid glycation during cataract formation.

    Science.gov (United States)

    Cheng, R; Lin, B; Lee, K W; Ortwerth, B J

    2001-07-27

    chromophores in brunescent lenses represent advanced glycation endproducts (AGEs) probably due to ascorbic acid glycation in vivo.

  15. 糖基化终末产物及其受体在胃肠道中的分布%Distribution of advanced glycation end products and their receptor in the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    陈朋民; 赵静波; Hans Gregersen

    2012-01-01

    目的:研究糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在胃肠道中的分布,为进一步探索其在慢性糖尿病胃肠功能紊乱中的作用奠定基础.方法:分别对成年Wistar大鼠食管、胃、十二指肠、空肠、回肠、结肠及直肠组织进行AGE及RAGE免疫组织化学染色.结果:(1)食管:AGE及RAGE主要分布在横纹肌的肌细胞及黏膜的鳞状上皮细胞;(2)胃:AGE在壁细胞为强阳性.RAGE在主细胞、肥大细胞、神经细胞为强阳性,在壁细胞为中等强度阳性,在表面黏液细胞为弱阳性;(3)小肠:AGE及RAGE在绒毛及固有层上皮细胞为阳性或强阳性.RAGE在肠道的神经细胞亦为强阳性;(4)结肠及直肠:AGE及RAGE在黏膜上皮细胞为弱阳性,RAGE在神经细胞为强阳性.结论:AGE及RAGE广泛分布于肠道上皮细胞及食管的横纹肌细胞,AGE亦分布于胃的壁细胞,RAGE亦分布于胃的壁细胞、主细胞、表面黏液细胞、肥大细胞及胃肠道的神经细胞.%AIM: To investigate the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the gastrointestinal (GI) tract to provide a basis for further study of the association between AGE/RAGE and diabetic GI dysfunction. METHODS: The distribution of AGEs [N epsilon-(c arboxymethyl) lysine and N epsilon-(carboxyethyl) lysine] and RAGE were detected in the esopha-geal, gastric, duodenal, jejunal, ileal, colonic and rectal tissues of normal adult Wistar rats using immunohistochemistry. RESULTS: In the esophagus, AGEs and RAGE were mainly distributed in striated muscle cells and squamous epithelial cells. In the stomach, AGEs were mainly distributed in parietal cells, and RAGE was strongly expressed in chief cells, mast cells and neurons in ganglia, moderately in parietal cells, and mildly in surface mucous cells. In the intestine, colon and rectum, AGEs and RAGE were distributed in mucosal

  16. Potent protein glycation inhibition of plantagoside in Plantago major seeds.

    Science.gov (United States)

    Matsuura, Nobuyasu; Aradate, Tadashi; Kurosaka, Chihiro; Ubukata, Makoto; Kittaka, Shiho; Nakaminami, Yuri; Gamo, Kanae; Kojima, Hiroyuki; Ohara, Mitsuharu

    2014-01-01

    Plantagoside (5,7,4',5'-tetrahydroxyflavanone-3'-O-glucoside) and its aglycone (5,7,3',4',5'-pentahydroxyflavanone), isolated from a 50% ethanol extract of Plantago major seeds (Plantaginaceae), were established to be potent inhibitors of the Maillard reaction. These compounds also inhibited the formation of advanced glycation end products in proteins in physiological conditions and inhibited protein cross-linking glycation. These results indicate that P. major seeds have potential therapeutic applications in the prevention of diabetic complications. PMID:24895551

  17. Potent Protein Glycation Inhibition of Plantagoside in Plantago major Seeds

    Directory of Open Access Journals (Sweden)

    Nobuyasu Matsuura

    2014-01-01

    Full Text Available Plantagoside (5,7,4′,5′-tetrahydroxyflavanone-3′-O-glucoside and its aglycone (5,7,3′,4′,5′-pentahydroxyflavanone, isolated from a 50% ethanol extract of Plantago major seeds (Plantaginaceae, were established to be potent inhibitors of the Maillard reaction. These compounds also inhibited the formation of advanced glycation end products in proteins in physiological conditions and inhibited protein cross-linking glycation. These results indicate that P. major seeds have potential therapeutic applications in the prevention of diabetic complications.

  18. Association of advanced glycation end products with A549 cells, a human pulmonary epithelial cell line, is mediated by a receptor distinct from the scavenger receptor family and RAGE.

    Science.gov (United States)

    Nakano, Nahoko; Fukuhara-Takaki, Kaori; Jono, Tadashi; Nakajou, Keisuke; Eto, Nobuaki; Horiuchi, Seikoh; Takeya, Motohiro; Nagai, Ryoji

    2006-05-01

    Cellular interactions with advanced glycation end products (AGE)-modified proteins are known to induce several biological responses, not only endocytic uptake and degradation, but also the induction of cytokines and growth factors, combined responses that may be linked to the development of diabetic vascular complications. In this study we demonstrate that A549 cells, a human pulmonary epithelial cell line, possess a specific binding site for AGE-modified bovine serum albumin (AGE-BSA) (K(d) = 27.8 nM), and additionally for EN-RAGE (extracellular newly identified RAGE binding protein) (K(d) = 118 nM). Western blot and RT-PCR analysis showed that RAGE (receptor for AGE) is highly expressed on A549 cells, while the expression of other known AGE-receptors such as galectin-3 and SR-A (class A scavenger receptor), are below the level of detection. The binding of (125)I-AGE-BSA to these cells is inhibited by unlabeled AGE-BSA, but not by EN-RAGE. In contrast, the binding of (125)I-EN-RAGE is significantly inhibited by unlabeled EN-RAGE and soluble RAGE, but not by AGE-BSA. Our results indicate that A549 cells possess at least two binding sites, one specific for EN-RAGE and the other specific for AGE-BSA. The latter receptor on A549 cells is distinct from the scavenger receptor family and RAGE.

  19. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

    Directory of Open Access Journals (Sweden)

    Jia You

    2016-01-01

    Full Text Available Advanced glycation end products (AGEs are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.

  20. Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-β expression and secretion.

    Science.gov (United States)

    Notsu, Masakazu; Yamaguchi, Toru; Okazaki, Kyoko; Tanaka, Ken-ichiro; Ogawa, Noriko; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2014-07-01

    In diabetic patients, advanced glycation end products (AGEs) cause bone fragility because of deterioration of bone quality. We previously showed that AGEs suppressed the mineralization of mouse stromal ST2 cells. TGF-β is abundant in bone, and enhancement of its signal causes bone quality deterioration. However, whether TGF-β signaling is involved in the AGE-induced suppression of mineralization during the osteoblast lineage remains unknown. We therefore examined the roles of TGF-β in the AGE-induced suppression of mineralization of ST2 cells and human mesenchymal stem cells. AGE3 significantly (P mineralization in both cell types, whereas transfection with small interfering RNA for the receptor for AGEs (RAGEs) significantly (P mineralization in both cell types. In contrast, SD208 intensified AGE3-induced suppression of cell proliferation as well as AGE3-induced apoptosis in proliferating ST2 cells. These findings indicate that, after cells become confluent, AGE3 partially inhibits the differentiation and mineralization of osteoblastic cells by binding to RAGE and increasing TGF-β expression and secretion. They also suggest that TGF-β adversely affects bone quality not only in primary osteoporosis but also in diabetes-related bone disorder.

  1. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPAR-γ). Although nifedipine did not affect expression levels of PPAR-γ, it increased the PPAR-γ transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-γ activation.

  2. Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training: influence of anti-inflammatory or glucosamine treatment.

    Science.gov (United States)

    Mattiello-Sverzut, Ana Claudia; Petersen, Susanne G; Kjaer, Michael; Mackey, Abigail L

    2013-09-01

    The aim of this study was to investigate the effect of 12-week resistance training on morphological presence of collagen and RAGE (receptor for advanced glycation end products) in skeletal muscle of patients with knee osteoarthritis (OA). Little is known about the influence of exercise on the skeletal muscle matrix that supports joints affected by OA mainly when it is associated with medication taken by OA patients (non-steroid anti-inflammatory drugs (NSAID) and glucosamine). A biopsy was collected from the vastus lateralis muscle in all patients before and after 12-week period of training. The patients (age 55-69 years) were divided into three groups, treated with NSAID, glucosamine or placebo. In addition, the muscle samples were analysed by immunohistochemistry for collagen types, RAGE and capillaries ratio. An increment in immunoreactivity for type IV collagen after the training period was observed in 72 % of all biopsies when compared with their respective baseline samples. Reduced immunoreactivity of collagen type I was observed in all patients treated with glucosamine. A significant increase with training in the amount of RAGE was detected in the placebo group only (p muscle fibres after 12 weeks of resistance training. Glucosamine with training appeared to attenuate RAGE accumulation more than was seen with NSAID or placebo in skeletal muscle of OA patients.

  3. Effects of candesartan cilexetil and amlodipine orotate on receptor for advanced glycation end products expression in the aortic wall of Otsuka Long-Evans Tokushima Fatty (OETFF) type 2 diabetic rats.

    Science.gov (United States)

    Kang, Min-Kyu; Chung, Woo-Baek; Hong, Seul-Ki; Kim, Ok-Ran; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

    2016-04-01

    The receptor for advanced glycation end products (RAGE) plays a key role in the development of vascular inflammation and acceleration of atherosclerosis in type 2 diabetes. We investigated the effect of candesartan cilexetil (CDRT) and amlodipine orotate (AMDP) on the expression of RAGE in the aortic walls of Otsuka Long-Evans Tokushima Fatty (OLETF) rats and AGE-treated endothelial cells. Twenty five-week-old OLETF rats were randomized to 8 week treatments consisting of CDRT (n = 8), AMDP (n = 8) or saline (control, n = 8). Immunohistochemical and dihydroethidine staining revealed reduced RAGE and reactive oxygen species (ROS) signals in rats treated with CDRT or AMDP compared with control rats. Both CDRT and AMDP suppressed the expression of p22phox and p47phox NADPH oxidase subunits. However, only CDRT significantly reduced expression of phosphorylated extracellular signal regulated kinase (pERK)1/2 in the aortic wall of OLETF rats. In addition, both drugs reduced RAGE expression and total and mitochondrial ROS production in the AGE-treated endothelial cells. Both ARBs and CCBs reduced RAGE expression in the aortic walls of OLETF rats, which was attributed to decreased ROS production through inhibition of NADPH oxidase. In addition, only CDRT reduced aortic expression of RAGE via suppression of the ERK1/2 pathway unlike AMDP. PMID:26960737

  4. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

    Science.gov (United States)

    You, Jia; Xu, Shiqing; Zhang, Wenjian; Fang, Qing; Liu, Honglin; Peng, Liang; Deng, Tingting

    2016-01-01

    Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.

  5. Using Serum Advanced Glycation End Products-Peptides to Improve the Efficacy of World Health Organization Fasting Plasma Glucose Criterion in Screening for Diabetes in High-Risk Chinese Subjects.

    Directory of Open Access Journals (Sweden)

    Zilin Sun

    Full Text Available The efficacy of using fasting plasma glucose (FPG alone as a preferred screening test for diabetes has been questioned. This study was aimed to evaluate whether the use of serum advanced glycation end products-peptides (sAGEP would help to improve the efficacy of FPG in diabetes screening among high-risk Chinese subjects with FPG <7.0 mmol/L. FPG, 2-h plasma glucose (2h-PG, serum glycated haemoglobin A1c (HbA1c, and sAGEP were measured in 857 Chinese subjects with risk factors for diabetes. The areas under receiver operating characteristic (ROC curves generated by logistic regression models were assessed and compared to find the best model for diabetes screening in subjects with FPG <7.0 mmol/L. The optimal critical line was determined by maximizing the sum of sensitivity and specificity. Among the enrolled subjects, 730 of them had FPG <7.0 mmol/L, and only 41.7% new diabetes cases were identified using the 1999 World Health Organization FPG criterion (FPG ≥7.0 mmol/L. The area under ROC curves generated by the model on FPG-sAGEP was the largest compared with that on FPG-HbA1c, sAGEP, HbA1c or FPG in subjects with FPG <7.0 mmol/L. By maximizing the sum of sensitivity and specificity, the optimal critical line was determined as 0.69×FPG + 0.14×sAGEP = 7.03, giving a critical sensitivity of 91.2% in detecting 2h-PG ≥11.1 mmol/L, which was significantly higher than that of FPG-HbA1c or HbA1c. The model on FPG-sAGEP improves the efficacy of using FPG alone in detecting diabetes among high-risk Chinese subjects with FPG <7.0 mmol/L, and is worth being promoted for future diabetes screening.

  6. Role of Glyoxalase 1 (Glo1 and methylglyoxal (MG in behavior: recent advances and mechanistic insights

    Directory of Open Access Journals (Sweden)

    Margaret G Distler

    2012-11-01

    Full Text Available Glyoxalase 1 (GLO1 is a ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MG, a cyotoxic byproduct of glycolysis that induces protein modification (advanced glycation end-products, AGEs, oxidative stress, and apoptosis. The concentration of MG is elevated under high-glucose conditions, such as diabetes. As such, GLO1 and MG have been implicated in the pathogenesis of diabetic complications. Recently, findings have linked GLO1 to numerous behavioral phenotypes, including psychiatric diseases (anxiety, depression, schizophrenia, and autism and pain. This review highlights GLO1’s association with behavioral phenotypes, describes recent discoveries that have elucidated the underlying mechanisms, and identifies opportunities for future research.

  7. Glycated hemoglobin and its spinoffs: Cardiovascular disease markers or risk factors?

    Institute of Scientific and Technical Information of China (English)

    Jumana; Saleh

    2015-01-01

    Atherosclerosis is a major complication of diabetes, increasing the risk of cardiovascular related morbidities and mortalities. The hallmark of diabetes is hyperglycemia which duration is best predicted by elevated glycated haemoglobin A1C(Hb A1C) levels. Diabetic complications are usually attributed to oxidative stress associated with glycation of major structural and functional proteins. This non-enzymatic glycation of long lived proteins such as collagen, albumin, fibrinogen, liver enzymes and globulins result in the formation of early and advanced glycation end products(AGEs) associated with the production of myriads of free radicles and oxidants that have detrimental effects leading to diabetic complications. AGEs have been extensively discussed in the literature as etiological factors in the advancement of atherogenic events. Mechanisms described include the effects of glycation on protein structure and function that lead to defective receptor binding, impairment of immune system and enzyme function and alteration of basement membrane structural integrity. Hemoglobin(Hb) is a major circulating protein susceptible to glycation. Glycated Hb, namely Hb A1 C is used as a useful tool in the diagnosis of diabetes progression. Many studies have shown strong positive associations between elevated Hb A1 C levels and existing cardiovascular disease and major risk factors. Also, several studies presented Hb A1 C as an independent predictor of cardiovascular risk. In spite of extensive reports on positive associations, limited evidence is available considering the role of glycated Hb in the etiology of atherosclerosis. This editorial highlights potential mechanisms by which glycated hemoglobin may contribute, as a causative factor, to the progression of atherosclerosis in diabetics.

  8. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp; Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp; Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp; Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp

    2015-05-29

    In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-kB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs, but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10{sup −8} M human parathyroid hormone (PTH)-(1–34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.

  9. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells.

    Science.gov (United States)

    Tanaka, Ken-ichiro; Yamaguchi, Toru; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2015-05-29

    In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-кB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs, but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10(-8) M human parathyroid hormone (PTH)-(1-34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. PMID:25721666

  10. Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

    Directory of Open Access Journals (Sweden)

    Grażyna E Sroga

    Full Text Available To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation or ribose (ribosylation. Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women. More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples. Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar

  11. Cinnamic Acid and Its Derivatives Inhibit Fructose-Mediated Protein Glycation

    OpenAIRE

    Sirintorn Yibchok-anun; Sirichai Adisakwattana; Weerachat Sompong; Sathaporn Ngamukote; Aramsri Meeprom

    2012-01-01

    Cinnamic acid and its derivatives have shown a variety of pharmacologic properties. However, little is known about the antiglycation properties of cinnamic acid and its derivatives. The present study sought to characterize the protein glycation inhibitory activity of cinnamic acid and its derivatives in a bovine serum albumin (BSA)/fructose system. The results demonstrated that cinnamic acid and its derivatives significantly inhibited the formation of advanced glycation end products (AGEs) by...

  12. Glycated albumin is an optimal biomarker for gestational diabetes mellitus

    OpenAIRE

    HUANG, YAPING; Hu, Yongwei; Ma, Yu; YE, GUANGYONG

    2015-01-01

    Gestational diabetes mellitus (GDM) refers to abnormal glucose tolerance, which is a common complication that occurs in some women for the first time during the gestation period. However, the relationship between onset of GDM and factors including advanced age and a family history of diabetes remains to be determined. The study aimed to examine the clinical significance of the detection of glycated albumin (GA) in pregnant women with GDM. A total of 893 cases of pregnant women with GDM were i...

  13. ANTI-GLYCATION EFFECT OF WHITTON ROOT (EULOPHIA NUDA IN-VITRO CONDITION

    Directory of Open Access Journals (Sweden)

    Dinesh Prasad Yadav et al

    2012-09-01

    Full Text Available Non enzymatic glycation takes place when elevated levels of reduced sugars react with amino groups of proteins and is called as advanced glycation end products (AGEs are responsible for Diabetes Mellitus. Hydroalcoholic extract of Whitton root (Eulophia nuda was tested for in-vitro inhibition of non-enzymatic glycation of Immunoglobin G. Plant extracts have their own importance and now being studied extensively due to having little or no side effects in all aspects of life sciences from botany to medicine in biochemical research. In present study Whitton root was selected and used to check the glycation inhibitory activity in-vitro condition. Various combinations of glucose, protein and Whitton root extracts were made under in vitro conditions and their activity was monitored with Trichloro acetic acid treatment method at 350 nm. Glycated products/ AGEs were more with high glucose and high protein concentration and these were decreased by highest concentration of Whitton root extract i.e. 30 mg/mL or 300 μL. Lower concentrations of plant extract produced either no or least response against advanced glycation end products (AGEs.

  14. [Analysis of the impact of heparin on the affinity of high mobility group box-1 protein and the receptor of advanced glycation end products by surface plasmon resonance technology].

    Science.gov (United States)

    Ling, Yan; Wang, Chun-You; Yang, Zhi-Yong

    2009-11-01

    To investigate the affinity constants of heparin with high mobility group protein 1(HMGB1) and HMGB1 with the receptor of advanced glycation end products (RAGE) and to analyze the impact of heparin on the affinity of HMGB1 and RAGE, the standard BIAcore amine coupling chemistry protocol using EDC and NHS was employed for immobilizing. Surface plasmon resonance biosensor technology was used to detect the affinity constants of heparin/HMGB1, HMGB1/RAGE and heparin/ RAGE. Binding analysis was used to investigate the impact of heparin on the affinity of HMGB1 and RAGE. After the immobilization, 9 000 and 5 000 RU rise of HMGB1 and RAGE respectively were obtained. These meant that the immobilized values of HMGB1 and RAGE were about 9 and 5 ng x mm(-2) respectively. The kinetic constants were k(a) = 1.78 x 10(5) L x mol(-1) x s(-1), kd = 8.02 x 10(-4) s(-1), and the affinity constants were KA = 2.22 x 10(8) L x mol(-1), the equilibrium dissociation constant K(D) = 4.5 x 10(-9) mol x L(-1) for heparin and HMGB1; while the kinetic constants were k(a) = 1.85 x 10(3) L x mol(-1) x s(-1), k(d) = 1.81 x 10(-4) s(-1), K(A) = 1.02 x 10(7) L x mol(-1), K(D) = 9.77 x 10(-8) mol x L(-1) for HMGB1 and RAGE; there was very low affinity of heparin with RAGE. The highest concentration of 10 000 u x L(-1) of heparin in this experiment did not reach the saturation with HMGB1. After 50 mg x L(-1) of HMGB1 was mixed with heparin of 50, 100, 1 000, 10 000 u x L(-1), the combining amount of HMGB1 and RAGE declined from 100 to 50 RU. But there were no significant differences between different concentrations of heparin. It was concluded that heparin can combine with HMGB1 and affect the affinity of HMGB1/RAGE. In addition, this impact was not in a dose-dependent manner. PMID:20101991

  15. Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE-independent signaling pathways and regulating mitochondrion-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Liu Rui

    2012-09-01

    Full Text Available Abstract Background It is known that amyloid-β peptide (Aβ plays a pivotal role in the pathogenesis of Alzheimer's disease (AD. Interaction between Aβ and the receptor for advanced glycation end products (RAGE has been implicated in neuronal degeneration associated with this disease. Pinocembrin, a flavonoid abundant in propolis, has been reported to possess numerous biological activities beneficial to health. Our previous studies have demonstrated that pinocembrin has neuroprotective effects on ischemic and vascular dementia in animal models. It has been approved by the State Food and Drug Administration of China for clinical use in stroke patients. Against this background, we investigated the effects of pinocembrin on cognitive function and neuronal protection against Aβ-induced toxicity and explored its potential mechanism. Methods Mice received an intracerebroventricular fusion of Aβ25-35. Pinocembrin was administrated orally at 20 mg/kg/day and 40 mg/kg/day for 8 days. Behavioral performance, cerebral cortex neuropil ultrastructure, neuronal degeneration and RAGE expression were assessed. Further, a RAGE-overexpressing cell model and an AD cell model were used for investigating the mechanisms of pinocembrin. The mechanisms underlying the efficacy of pinocembrin were conducted on target action, mitochondrial function and potential signal transduction using fluorescence-based multiparametric technologies on a high-content analysis platform. Results Our results showed that oral administration of pinocembrin improved cognitive function, preserved the ultrastructural neuropil and decreased neurodegeneration of the cerebral cortex in Aβ25-35-treated mice. Pinocembrin did not have a significant effect on inhibiting Aβ1-42 production and scavenging intracellular reactive oxygen species (ROS. However, pinocembrin significantly inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and also markedly

  16. 银杏叶提取物对AGEs诱导的大鼠HSC增殖的抑制作用%The effect of ginko biloba extract on proliferation of hepatic stellate cell activating by advanced glycation end products

    Institute of Scientific and Technical Information of China (English)

    史美娜; 栗华

    2013-01-01

    目的:探讨不同浓度晚期糖基化终产物(AGEs)对体外培养的大鼠肝星状细胞(HSC)增殖的影响,并观察不同浓度银杏叶提取物(EGb)对其增殖有无抑制作用。方法体外合成AGEs,MTT法观察不同浓度的AGEs对HSC增殖的影响及不同浓度EGb对AGEs促HSC增殖的抑制作用。结果当培养液中AGEs浓度≥50mg/L时,12~48h内检测发现HSC较正常对照组增殖明显并呈时间及剂量依赖性(P<0.05),而6h内及低浓度AGEs组未观察到其对HSC增殖有明显影响。EGb在培养48h时对AGEs刺激的HSC的增殖有显著抑制作用(P<0.05),且呈明显的剂量依赖性。结论 AGEs可以促进HSC增殖,呈时间、剂量依赖性;在作用时间充分的前提下,EGb可抑制AGEs诱导的HSC增殖,呈剂量依赖性。%Objective To investigate the effect of ginko biloba extract (EGb) on the cell proliferation in HSC stimulated by advanced glycation end products(AGEs). Methods AGEs was synthesized by incubating glucose with BSA in vitro. MTT colorimetric assay was used to observe the effect of AGEs at different dosages on the proliferation of HSC,and to measure the effect of EGb at different dosages on the proliferation of HSC.Results The proliferation of HSC was enhanced after incubating with ≥50mg/L AGEs for 12-48 hour with a dose and time dependent manner but within 6 hour(P<0.05). The low concentration of AGEs group which was not observed a significant effect on the proliferation of HSC. The proliferation of HSC was slow and exhibited a dose dependent manner with 48 hour treatment of EGb. Conclusion EGb depressed the proliferation of HSC which is induced by AGEs with a dose and time dependant manner.

  17. Expressions of advanced glycation end products and their receptors in keloid%晚期糖基化终末产物及其受体在瘢痕疙瘩中的表达

    Institute of Scientific and Technical Information of China (English)

    石磊; 陈晓栋; 杨圣菊; 顾黎雄; 孟国梁

    2010-01-01

    Objective To investigate the expressions of advanced glycation end products (AGEs) and their receptors in keloid. Methods Serum and skin tissue specimens were collected from 20 patients with keloid, 20 patients with hyperplastic scar and 20 normal human controls. Fluorospectrophotometer was used to measure the serum level of AGEs, and immunohistochemistry and Western blotting to detect the expressions of AGEs and AGER in skin tissue specimens. Results The serum level of AGEs was (0.713 ± 0.098) AU/ml and (0.699 ± 0.077) AU/ml respectively in patients with keloid and those with hypertrophic scar, significantly higher than that in normal controls (0.179 ± 0.056 AU/ml, F = 283.82, P 0.05). Conclusion There is a high expression of AGEs and AGER in keloid, which may contribute to the development of keloid.%目的 研究晚期糖基化终末产物(AGE)及其受体(AGER)在瘢痕疙瘩中的表达.方法 瘢痕疙瘩、增生性瘢痕和正常人群血清、皮肤组织标本各20份,以荧光分光光度计检测三组人群血清中AGE含量,分别采用免疫组化法、Western印迹分析检测三组人群皮肤组织标本中AGE和AGER表达情况.结果 瘢痕疙瘩组血清中AGE含量为(0.713±0.098)AU/ml,增生性瘢痕组为(0.699±0.077)AU/ml,明显高于正常人群组(0.179±0.056)AU/ml,三组差异有统计学意义(F=283.82,P0.05).结论 AGE和AGER在瘢痕疙瘩中表达升高,在其发病过程中可能发挥一定的促进作用.

  18. Inhibition of glucose- and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

    Institute of Scientific and Technical Information of China (English)

    Jugjeet Singh Ramkissoon; Mohamad Fawzi Mahomoodally; Anwar Hussein Subratty; Nessar Ahmed

    2016-01-01

    Objective: To investigate the inhibitory activity of ten culinary herbs and spices namely on glucose-mediated glycation (GMG) and fructose-mediated glycation (FMG) of bovine serum albumin. Methods: Fluorescence was used as an index of albumin glycation using glucose and fructose as substrates in the presence of infusions and ethanolic extracts of ten culinary herbs and spices. Antioxidant activity of the extracts was evaluated using reducing power, metal ion chelating and superoxide radical scavenging assays. Phytochemicals profile was analysed using 13 standard methods. Results: FMG was found to be significantly higher than GMG (95 and 84 AU, respectively; P 0.05) was found in the percentage glycation inhibitory activity of infusions compared to ethanolic extracts. The mean percentage inhibitory activity of the extracts for GMG (45.9%) and for FMG (45.1%) was not significantly different (P > 0.05). Qualitative phytochemical analysis showed the presence of alkaloids, fla-vonoids, tannins, terpenoids, anthraquinones, steroids, reducing sugars, proteins, phenols, saponins, phlobatannins, and cardiac glycosides. Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation end-products-mediated complications.

  19. 晚期糖基化终产物与冠心病发病机制的研究进展%Research on advanced glycation end products in the mechanism of coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    刘军锋; 孔美娟; 贾克刚

    2014-01-01

    晚期糖基化终产物(AGEs)密切参与了血管平滑肌细胞(VSMCs)分化与增殖以及冠心病等心血管疾病的病理生理过程。AGEs能通过单核细胞趋化蛋白(ERK)、丝氨酸/苏氨酸蛋白激酶(Akt)信号通路来诱导VSMCs的自噬作用,可依赖骨髓基质细胞衍生因子-1(SDF-1)/趋化因子受体CXCR4轴信号通路促进心肌微血管内皮细胞(CMECs)的增生。AGEs-2和AGEs-3上调了单核细胞AGEs受体(RAGE)的表达。AGEs能抑制内皮祖细胞(EPCs)的增殖、迁移和黏附功能并诱导EPCs凋亡;能增加平滑肌细胞结缔组织因子(CTGF)mRNA和蛋白质的表达,刺激心肌成纤维细胞增殖并分泌转化生长因子-β1(TGF-β1),同时诱导Smad2及Smad4的表达。羧甲基赖氨酸(CML)/RAGE轴通过主动脉平滑肌成骨细胞的分化,诱导巨噬细胞凋亡,从而使AGEs在糖尿病动脉粥样硬化中发挥重要作用。可溶性RAGE(sRAGE)可作为RAGE配体的诱饵来防止动脉粥样硬化,其灵敏度和阴性预测值在判定冠状动脉介入治疗(PCI)术后再狭窄方面均高于AGEs/sRAGE比值。ALT-711是一种AGEs的裂解剂,能明显抑制AGEs介导的活性氧(ROS)产生、细胞外信号调节激酶磷酸化及环氧合酶-2的表达;色素上皮衍生因子(PEDF)能抑制AGEs诱导的血小板CD40配体(CD40L)表达,从而有可能成为预防冠心病的一个治疗靶点。他汀类药物亦能抑制AGEs诱导主动脉平滑肌细胞的增殖及ROS的产生。通过以上诸多因素的研究,可揭示冠心病的某些发病机制,为相应干预药物的研究及调整临床治疗策略提供依据和方向。%Advanced glycation end products (AGEs)are closely involved in the pathophysiological process of vascular smooth muscle cell (VSMCs)differentiation,proliferation,coronary artery disease and other cardiovascular diseases.AGEs can induce autophagy in VSMCs through the

  20. Effect of advanced glycation end products on renin-angiotensin system in podocytes%晚期糖基化终产物对足细胞内肾素-血管紧张素系统的影响

    Institute of Scientific and Technical Information of China (English)

    成彩联; 郑振达; 石成钢; 叶增纯; 刘迅; 娄探奇

    2013-01-01

    Objective To investigate the effect and mechanism of advanced glycation end products (AGEs) on the components of renin-angiotensin system (RAS) in the podocytes.Methods Immortalized mouse podocytes were exposed to various concentrations of AGEs for 24 h.The expression levels of renin,angiotensinogen (AGT) and angiotensin Ⅱ type 1 and 2 receptors (AT1R and AT2R),the level of angiotensin Ⅱ (Ang Ⅱ),and the activity of angiotensin-converting enzyme (ACE) were assayed.The levels of Akt and phosphorylated Akt were examined by Western blotting.Cell adhesion was measured in the podocytes pretreated with phosphoinositide 3-kinase (PI3-K) inhibitor LY294002,losartan,captopril and chymostatin,respectively.Results Treatment with AGEs resulted in significant increase in the expression of AGT and AT1R.Moreover,ACE activity and Ang Ⅱ level increased significantly.However,there was no significant change in renin and AT2R expression.AGEs increased the phosphorylation of Akt by 100%.When the podocytes were pretreated with LY294002 (10 μmol/L),the AGEs-induced increase in AGT and AT1R expression reduced remarkably.Likewise,ACE activity and Ang Ⅱ level decreased significantly,and the reduced podocyte adhesive capacity induced by AGEs was improved significantly.Conclusions AGEs activate the RAS via PI3-K/Akt-dependent pathway,and lead to a decrease in podocyte adhesion.%目的 观察晚期糖基化终产物(advanced glycation end products,AGEs)对足细胞内肾素-血管紧张素系统(renin-angiotensin system,RAS)的影响及作用机制.方法 不同浓度的AGEs干预小鼠足细胞24h,分别检测肾素(renin)、血管紧张素原(renin-angiotensin system,AGT)、血管紧张素Ⅱ1型、2型受体(AT1R、AT2R)的表达,血管紧张素转换酶(angiotensin-converting enzyme,ACE)的活性和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)的浓度,观察蛋白激酶B(Akt)的磷酸化,然后分别加入磷酸肌醇3激酶抑制剂LY294002、Iosartan、captopril和chymastatin,

  1. Effect of C-peptide on advanced glycation end products-induced oxidative stress in rat mesangial cells%C肽对晚期糖基化终末产物诱导的大鼠肾小球系膜细胞氧化应激的影响

    Institute of Scientific and Technical Information of China (English)

    许世清; 张文健; 刘虹麟; 娄晋宁; 王在; 彭亮; 房青; 游嘉; 邓婷婷; 郭彬

    2015-01-01

    Objective To investigate the effect of C-peptide on advanced glycation end products (AGE)-induced oxidative stress in rat mesangial cells and its mechanism. Methods Rat mesangial cells were cultured in the normal medium(Control group),or medium with 200 mg/L AGEs(AGEs group),or medium with 200 mg/L AGEs and 5μmol/L C-peptide(AGEs+C-peptide group)or medium with 10μmol/L H89(added in advance,and incubated for 30 min)and 200 mg/L AGEs and 5μmol/L C-peptide(AGEs+C-peptide+H89 group). The intracellular reactive oxygen species(ROS)was detected with fluorescence method,and the supernatant nitric oxide(NO)level was detected by Griess reaction. Real-time PCR and Western blotting were used to detect the expression of the receptor for advanced glycation endproducts (RAGE),protein kinase A(PKA),nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)and inducible nitric oxide synthase(iNOS). Non-parametric Kruskal-Wallis H test and Mann-Whitney U test were used to compare data between groups,and two groups,respectively. Results Compared with control group,the level of ROS and NO increased in AGEs group(193.7±6.4 vs 136.1±4.9;and 27.2±4.7 vs 15.5± 0.7,respectively,all U=0,P<0.05). C-peptide could suppress the production of ROS and NO. In AGEs+C-peptide group,ROS and NO reduced than AGEs group(136.9±14.3 vs 193.7±6.4 and 16.0±2.1 vs 27.2±4.7 respectively,all U=0,P<0.05). Compared with control group,AGEs could up-regulate the expression of RAGE(0.565±0.027 vs 0.148±0.006,U=0,P<0.05)but down-regulate PKA(0.085±0.035 vs 0.518±0.019, U=0,P<0.05). And AGEs increased the expression of NOX4 and iNOS(0.912±0.055 vs 0.105±0.012,and 0.279±0.003 vs 0.126±0.004 respectively,all U=0,P<0.05). Compared with AGEs group,C-peptide down-regulated RAGE(0.159 ± 0.003 vs 0.565 ± 0.027,U=0,P<0.05),up-regulated PKA(0.594 ± 0.079 vs 0.085 ± 0.035,U=0,P<0.05),and down-regulated NOX4 and iNOS(0.085±0.005 vs 0.912±0.055,and 0.071±0.016 vs 0.279 ± 0.003 respectively,all U=0,P<0

  2. Effects of advanced glycation end-products on the expression of GLP-1 receptor and apopotis in cultured cardiomyocytes%糖基化终产物对心肌细胞GLP-1受体表达及凋亡影响的研究

    Institute of Scientific and Technical Information of China (English)

    胡波; 李德才

    2013-01-01

    目的 探讨糖基化终产物(AGEs)对乳鼠心肌细胞胰高血糖素样肽1受体(GLP-1R)、caspase-3表达及凋亡的影响.方法 原代培养乳鼠心肌细胞,以不同浓度葡萄糖孵育的糖化清蛋白(AGE-BSA)干预24h和同一浓度葡萄糖孵育的AGE-BSA干预24~72h,检测其对心肌细胞GLP-1RmRNA、活化的caspase-3表达及凋亡的影响.结果 AGE-BSA 可抑制心肌细胞GLP-1RmRNA表达,并诱导细胞caspase-3表达,凋亡增加.各AGE-BSA 组间及与对照组比较差异有统计学意义(P<0.05).结论 AGE-BSA 能抑制心肌细胞GLP-1RmRNA表达,并诱导细胞caspase-3表达,增加细胞凋亡,提示糖基化终产物在糖尿病心肌病的发生中可能具有重要的作用.

  3. Advanced glycation end-products decreases THP-1 macrophages expression of peroxisome proliferator activated receptor-γ%糖基化终产物抑制THP-1巨噬细胞过氧化物酶体增殖物激活受体γ的表达

    Institute of Scientific and Technical Information of China (English)

    杨启红; 徐强; 张红; 司良毅

    2008-01-01

    目的:观察糖基化终产物(AGEs)对THP-1巨噬细胞过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响,探讨AGEs在糖尿病动脉粥样硬化中可能的作用.方法:用佛波酯(PMA)诱导THP-1单核细胞72h使其分化为巨噬细胞,并将糖基化-牛血清白蛋白(AGE-BSA)与巨噬细胞共同孵育,运用RT-PCR和免疫细胞化学法分别检测巨噬细胞PPARγ mRNA和蛋白的表达水平.结果:PMA诱导72h后,THP-1细胞停止增殖,由单核细胞分化成为巨噬细胞.50、100、200和400μg/mlAGE-BSA处理24h后,巨噬细胞PPARγ mRNA相对表达量分别是1.235±0.044、0.752±0.055、0.494±0.026、0.277±0.025;PPARγ蛋白的平均积分光密度值分别为36.460±0.625、24.561±0.636、19.326±0.803、12.715±0.752,二者较100μg/ml牛血清白蛋白(BSA)组均明显降低(P<0.05).200μg/ml AGE-BSA作用12、24、36和48h后,巨噬细胞PPARγ mRNA相对表达量分别是1.564±0.060、1.260±0.043、0.467±0.033、0.360±0.012;PPARγ蛋白的平均积分光密度值分别为32.502±0.739、22.234±0.835、16.568±0.683、11.537±0.547,二者较0h组也明显降低(P<0.05 o结论:AGEs可下调THP-1巨噬细胞PPARγmRNA和蛋白的表达水平,且呈浓度和时间依赖性.

  4. 糖基化终末产物抑制骨髓间充质干细胞功能的机制%Mechanism of advanced glycation end products inhibiting function of bone mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    孟宪丽; 孟华; 陈岩

    2016-01-01

    Objective To explore the mechanism of advanced glycation end products (AGEs) attenuating the proliferation and migration in mesenchymal stem cells (MSCs).Methods The MSCs were isolated from male Sprague Dawley rats,and identified by flow cytometry (positive:CD29 and CD90;negative:CD34 and CD45).MSCs were stimulated by AGEs-bovine serum albumin (BSA) with different doses (0,25,50,100 and 200 mg/L) and time (6,12 and 24 h).The proliferation of cells was examined by methyl thiazol tetrazolium (MTT) assay.Wound-healing assay was used to assess the migration potential of cells treated with AGEs-BSA.Intracellular formation of reactive oxygen species (ROS) was evaluated using a fluorescent probe.Results The relative metabolic activity was significantly reduced by 81.22%,80.53% and 51.50% with AGEs-BSA (200 mg/L) at 6,12,and 24 h,respectively.The proliferation potential of MSCs was impacted by AGEs-BSA in a dose-and time-dependent manner.AGEs-BSA (200 mg/L for 24 h) obviously inhibited migration of MSCs [(0.012 ±0.006) μm/min vs.(0.022-±0.002) μm/min,P <0.01].At the same time,AGEs-BSA significantly induced the intracellular ROS accumulation.Conclusion AGEs-BSA induced ROS formation via receptor to inhibit proliferation and migration.%目的 探讨糖基化终末产物(AGEs)对间充质干细胞(MSCs)增殖和迁移能力的影响及其机制.方法 体外培养SD大鼠MSCs,流式细胞术鉴定阳性指标(CD29和CD90)和阴性指标(CD34和CD45).噻唑蓝(MTT)比色法检测不同剂量(0、25、50、100、200 mg/L) AGEs-牛血清白蛋白(BSA)在刺激不同时间(6、12、24h)后MSCs增殖变化.采用Wound-healing划痕实验检测不同剂量(0、25、50、100、200 mg/L) AGEs-BSA刺激骨髓间充质干细胞24h后的迁移能力.荧光染色拍照测定AGEs-BSA(200 mg/L)刺激12、24h后细胞内活性氧(ROS)累积情况.结果 200 mg/L AGEs-BSA刺激6、12、24 h MSCs增殖能力显著下降,分别为81.22%、80.53%、51.50%,AGEs-BSA抑制细胞

  5. Apoptosis of rat periodontal ligament fibroblasts induced by advanced glycation end products and its receptor%糖基化终产物及其受体对牙周膜成纤维细胞凋亡影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    邓天政; 吕晶; 冯岩; 李冬霞; 刘冰; 逄键梁; 臧晓霞; 柯杰

    2012-01-01

    目的 观察糖基化终产物(advanced glycation end products,AGE)促进糖基化终产物受体(receptor for advanced glycation end products,RAGE)在大鼠牙周膜成纤维细胞(periodontal ligament fibroblasts,PDLF)中的表达情况,并研究RAGE在大鼠PDLF凋亡中的作用.方法 第3代大鼠PDLF在含有终浓度为200 mg/L的糖基化牛血清白蛋白(advanced glycation end products-bovine serum albumin,AGE-BSA)培养基内培养,根据孵育时间分为实验组A1、A2、A3、A4组;相同条件下PDLF于终浓度200 mg/L的BSA孵育,按与A1 ~ A4组相同的孵育时间分为实验组B1、B2、B3、B4;在无AGE-BSA、BSA的培养基内培养第3代PDLF设为对照组C组.检测各组细胞活性、细胞凋亡情况、RAGE及细胞凋亡蛋白酶3 mRNA表达情况.结果 AGE干预的大鼠PDLF在细胞形态学及细胞活性检测方面均发生改变.相同时间点A、B各组细胞活性组间比较差异具有统计学意义(P<0.01),A1、A2、A3、A4 4组细胞活性的组间差异无统计学意义(F=2.353,P=0.088),B1、B2、B3、B44组的组间差异亦无统计学意义(F=0.468,P=0.706).经流式细胞术检测,实验组A1、A2、A3、A4组细胞凋亡比例依次明显增高,与C组比较差异具有统计学意义(P<0.01).受AGE干预的细胞可以表达RAGE且细胞凋亡蛋白酶3表达阳性.结论 AGE可以刺激大鼠PDLF表达RAGE,促进细胞凋亡.%Objective To detect receptor for advanced glycation end products expression level produced in rat periodontal ligament fibroblasts cultured in vitro, and to evaluate the mechanism of apoptosis in this progress. Methods Rat periodontal ligament fibroblasts induced by advanced glycation end products-bovine serum albumin (AGE-BSA) and bovine serum albumin (BSA) , were collected and were devided into 8 groups according to the intervention time in vitro, while no interventions is control group. The cell viability was evaluated with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H

  6. Comprehensive Identification of Glycated Peptides and Their Glycation Motifs in Plasma and Erythrocytes of Control and Diabetic Subjects

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Monroe, Matthew E.; Schepmoes, Athena A.; Clauss, Therese RW; Gritsenko, Marina A.; Meng, Da; Petyuk, Vladislav A.; Smith, Richard D.; Metz, Thomas O.

    2011-07-01

    Non-enzymatic glycation of proteins is implicated in diabetes mellitus and its related complications. In this report, we extend our previous development and refinement of proteomics-based methods for the analysis of non-enzymatically glycated proteins to comprehensively identify glycated proteins in normal and diabetic human plasma and erythrocytes. Using immunodepletion, enrichment, and fractionation strategies, we identified 7749 unique glycated peptides, corresponding to 3742 unique glycated proteins. Semi-quantitative comparisons revealed a number of proteins with glycation levels significantly increased in diabetes relative to control samples and that erythrocyte proteins are more extensively glycated than plasma proteins. A glycation motif analysis revealed amino acids that are favored more than others in the protein primary structures in the vicinity of the glycation sites in both sample types. The glycated peptides and corresponding proteins reported here provide a foundation for the potential identification of novel markers for diabetes, glycemia, or diabetic complications.

  7. Sri Lankan black tea (Camellia sinensis L.) inhibits the methylglyoxal mediated protein glycation and potentiates its reversing activity in vitro

    Institute of Scientific and Technical Information of China (English)

    Wanigasekara Daya Ratnasooriya

    2016-01-01

    Objective: To evaluate inhibitory activity of methylglyoxal (MGO) mediated protein glycation and ability to potentiate its reversing activity and range of antioxidant properties of Sri Lankan low grown orthodox orange pekoe grade black tea. Methods: Freeze dried black tea brew (BTB) was used as the sample in this study. Anti-glycation and glycation reversing activity was studied in bovine serum albumin (BSA)-MGO model. Antioxidant properties were studied using total polyphenolic content, total flavonoid content, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, 1,1-diphenyl-2-picrylhydrazine and ferric reducing antioxidant power in vitro antioxidant assays. Results: The results demonstrated significant (P Conclusions: The novel properties observed for Sri Lankan orange pekoe grade black tea indicate its usefulness as a supplementary beverage in managing MGO and advanced glycation end products related diseases and ailments.

  8. Sugar Sag: Glycation and the Role of Diet in Aging Skin.

    Science.gov (United States)

    Nguyen, H P; Katta, R

    2015-11-01

    First described in the context of diabetes, advanced glycation end products (AGEs) are formed through a type of non-enzymatic reaction called glycation. Increased accumulation of AGEs in human tissue has now been associated with end stage renal disease, chronic obstructive pulmonary disease, and, recently, skin aging. Characteristic findings of aging skin, including decreased resistance to mechanical stress, impaired wound healing, and distorted dermal vasculature, can be in part attributable to glycation. Multiple factors mediate cutaneous senescence, and these factors are generally characterized as endogenous (e.g., telomere shortening) or exogenous (e.g., ultraviolet radiation exposure). Interestingly, AGEs exert their pathophysiological effects from both endogenous and exogenous routes. The former entails the consumption of sugar in the diet, which then covalently binds an electron from a donor molecule to form an AGE. The latter process mostly refers to the formation of AGEs through cooking. Recent studies have revealed that certain methods of food preparation (i.e., grilling, frying, and roasting) produce much higher levels of AGEs than water-based cooking methods such as boiling and steaming. Moreover, several dietary compounds have emerged as promising candidates for the inhibition of glycation-mediated aging. In this review, we summarize the evidence supporting the critical role of glycation in skin aging and highlight preliminary studies on dietary strategies that may be able to combat this process. PMID:27224842

  9. Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes.

    Directory of Open Access Journals (Sweden)

    Pamela Maher

    Full Text Available The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE, serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.

  10. Preserving Brain Function in Aging: The Anti-glycative Potential of Berry Fruit.

    Science.gov (United States)

    Thangthaeng, Nopporn; Poulose, Shibu M; Miller, Marshall G; Shukitt-Hale, Barbara

    2016-09-01

    Advanced glycation end products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produced when those foods are cooked at high temperatures. Studies have linked AGEs to various age-related physiological changes, including wrinkles, diabetic complications, and neurodegenerative disease, including Alzheimer's disease. Dietary berry fruits have been shown to reduce the severity or slow the progression of many physiological changes and disease pathologies that accompany aging. Emerging evidence has shown that the phytochemicals found in berry fruits exhibit anti-glycative activity. In this review, we briefly summarize the current evidence supporting the neuroprotective anti-glycative activity of berry fruits and their potential to preserve cognitive function during aging. PMID:27166828

  11. 糖基化终产物对原代培养乳鼠肾脏细胞损伤的影响%The Effect of Advanced Glycation End Products on Primary Culture of Neonatal Rat Kidney Cells

    Institute of Scientific and Technical Information of China (English)

    叶希韵; 张再超; 刘江; 翁宇静; 童智

    2008-01-01

    The advanced glycation end products (AGEs) may play an important adverse role in process of diabetic nephropathy; however, the pathological mechanism can not be explained. This study aimed to investigate the effect of AGEs on primary cultured neonatal rat kidney cells and discussed the functional mechanism. The kidney cells were isolated from 3-day-old rats for in vitro primary culture, and the 4-6th generations of the cells culture were treated with AGEs at different concentrations (0, 1.2, 2.5, 5, 10, 20 mg/ml) and different times (6, 12, 18, 24 h). Cell proliferation was determined by methyl thiazolyl tetrazolium (MTT) method, and the enzyme-linked assay kit evaluated the extracellular concentration alteration of lactate dehydrogenase (LDH) and N-acetyl-β-Dglucosaminidase (NAG), and the intracellular concentration alteration of reduced glutathione (GSH) and superoxide dismutase (SOD) influenced by AGEs. The results suggest that, along with higher concentration and longer action time of AGEs, the cell livability, the intracellular concentration of GSH, and the SOD activity are gradually decreased, however, the concentrations of LDH and NAG in culture solution are significantly increased (P<0.001), compared with the control group. There is a significant concentration-effect relationship between the concentration and action time of AGEs. Our findings support that AGEs can significantly damage primary cultivated kidney cells, Moreover, the effect of AGEs on kidney cell is dose and time-dependent. Therefore, we conclude that kidney cells are sensitive to AGEs and the changes of cell permeability and antioxidant capacity induced by AGEs might be linked to the pathogenesis of diabetic nephropathy.%糖基化终产物(AGEs)在糖尿病肾病的发生发展过程中起着重要的作用.但目前其作用机制还不太清楚.通过体外乳鼠肾脏细胞的原代培养,探讨AGEs对肾细胞的损伤作用及可能的作用机制.取出生3天的SD大鼠的乳鼠肾

  12. Role of early glycation Amadori products of lysine-rich proteins in the production of autoantibodies in diabetes type 2 patients.

    Science.gov (United States)

    Ansari, Nadeem Ahmad; Moinuddin; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif; Khan, Rizwan Hasan

    2014-11-01

    In diabetes, protein glycation mostly occurs at intrachain lysine residues resulting in the formation of early stage Amadori products which are finally converted to advance glycation end products (AGEs). Several studies have reported autoantibodies against AGEs in diabetes but not much data are found in respect of Amadori products. In this study, poly-L-lysine (PLL) was glycated with 50 mM glucose and the resultant Amadori products were estimated by fructosamine or nitroblue tetrazolium assay. We report high content of Amadori products in PLL upon glycation. Glycated PLL showed marked hyperchromicity in the UV spectrum, ellipticity changes in CD spectroscopy, and variations in ε-methylene protons shift in NMR. It was better recognized by autoantibodies in type 2 diabetics compared to the native PLL. Induced antibodies against glycated PLL were successfully used to probe early glycation in the IgG isolated from diabetes type 2 patients. Role of Amadori products of glycated proteins in the induction of autoantibodies in type 2 diabetes as well as in associated secondary complications has been discussed.

  13. EFFECT OF SALEP (EULOPHIA CAMPESTRIS ON GLYCATION OF IgG IN-VITRO CONDITION

    Directory of Open Access Journals (Sweden)

    Yadav Dinesh Prasad

    2012-01-01

    Full Text Available Protein glycation takes place when elevated levels of reduced sugars react with amino groups in proteins, reaction known as Maillard reaction. If this process continues, it will lead to the formation of complex, often unstable, irreversible and reactive compounds Advanced Glycation End- Products (AGEs a process that may take weeks or even months to accomplish. Plant extracts have their own importance and now being studied extensively due to having little or no side effects. In present study salep was selected and used to check the glycation inhibitory activity. Various combinations of glucose, protein and salep extracts were made under in vitro conditions and their activity was monitored with Trichloro acetic acid treatment method at 350 nm. Glycated products/ AGEs were more with high glucose and high protein concentration and these were decreased by highest concentration of salep extract i.e. 25 mg/mL or 250 μL. Lower concentrations of plant extract produced either no or least response against Maillard reaction.

  14. Improved Methods for the Enrichment and Analysis of Glycated Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Schepmoes, Athena A; Brock, Jonathan W; Wu, Si; Moore, Ronald J; Purvine, Samuel O; Baynes, John; Smith, Richard D; Metz, Thomas O

    2008-12-15

    Non-enzymatic glycation of tissue proteins has important implications in the development of complications of diabetes mellitus. Herein we report improved methods for the enrichment and analysis of glycated peptides using boronate affinity chromatography and electron transfer dissociation mass spectrometry, respectively. The enrichment of glycated peptides was improved by replacing an off-line desalting step with an on-line wash of column-bound glycated peptides using 50 mM ammonium acetate. The analysis of glycated peptides by MS/MS was improved by considering only higher charged (≥3) precursor-ions during data-dependent acquisition, which increased the number of glycated peptide identifications. Similarly, the use of supplemental collisional activation after electron transfer (ETcaD) resulted in more glycated peptide identifications when the MS survey scan was acquired with enhanced resolution. In general, acquiring ETD-MS/MS data at a normal MS survey scan rate, in conjunction with the rejection of both 1+ and 2+ precursor-ions, increased the number of identified glycated peptides relative to ETcaD or the enhanced MS survey scan rate. Finally, an evaluation of trypsin, Arg-C, and Lys-C showed that tryptic digestion of glycated proteins was comparable to digestion with Lys-C and that both were better than Arg-C in terms of the number glycated peptides identified by LC-MS/MS.

  15. Open tubular capillary electrochromatography: A useful microreactor for collagen I glycation and interaction studies with low-density lipoprotein particles

    Energy Technology Data Exchange (ETDEWEB)

    D' Ulivo, Lucia; Witos, Joanna [Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FIN-00014 University of Helsinki (Finland); Ooerni, Katariina; Kovanen, Petri T. [Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki (Finland); Riekkola, Marja-Liisa, E-mail: marja-liisa.riekkola@helsinki.fi [Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FIN-00014 University of Helsinki (Finland)

    2010-04-07

    Diabetes, a multifunctional disease and a major cause of morbidity and mortality in the industrialized countries, strongly associates with the development and progression of atherosclerosis. One of the consequences of high level of glucose in the blood circulation is glycation of long-lived proteins, such as collagen I, the most abundant component of the extracellular matrix (ECM) in the arterial wall. Glycation is a long-lasting process that involves the reaction between a carbonyl group of the sugar and an amino group of the protein, usually a lysine residue. This reaction generates an Amadori product that may evolve in advanced glycation end products (AGEs). AGEs, as reactive molecules, can provoke cross-linking of collagen I fibrils. Since binding of low-density lipoproteins (LDLs) to the ECM of the inner layer of the arterial wall, the intima, has been implicated to be involved in the onset of the development of an atherosclerotic plaque, collagen modifications, which can affect the affinity of native and oxidized LDL for collagen I, can promote the entrapment of LDLs in the intima and accelerate the progression of atherosclerosis. In this study, open tubular capillary electrochromatography is proposed as a new microreactor to study in situ glycation of collagen I. The kinetics of glycation was first investigated in a fused silica collagen I-coated capillary. Dimethyl sulphoxide, injected as an electroosmotic flow marker, gave information about the charge of coating. Native and oxidized LDL, and selected peptide fragments from apolipoprotein B-100, the protein covering LDL particles, were injected as marker compounds to clarify the interactions between LDLs and the glycated collagen I coating. The method proposed is simple and inexpensive, since only small amounts of collagen and LDL are required. Atomic force microscopy images complemented our studies, highlighting the difference between unmodified and glycated collagen I surfaces.

  16. Inhibitory effect of litchi pericarp procyanidins on advanced glycation end products formation in model system ofα-Lactose/L-Lysine%荔枝皮原花青素对模拟食品体系中糖基化终产物的抑制效果

    Institute of Scientific and Technical Information of China (English)

    李书艺; 秦新光; 程吉祥; 祝振洲; 何静仁; 刘刚

    2016-01-01

    Industrial food processing induces protein glycation modifications and toxic advanced glycation end products (AGEs) which affect human health. Thus, it is an urgent problem in food process industry to control and inhibit the formation of AGEs during Maillard reaction. In this study, a model system consisting of lactose (as reducing disaccharide) and lysine (as very reactive amino acid) was established to monitor the AGE formation. Litchi pericarp procyanidins (LPPC), a natural antioxidant, was incubated in the simulated systems at different concentrations (0.02-0.10 mg/mL) and temperature levels (80 or 100℃) with or without various metal ions (Al3+, Ca2+, Fe2+, Cu2+, Mg2+ and Zn2+), which was to observe its inhibitory effect on AGEs. With all samples, the formation of fluorescent AGEs was quantitatively assessed using a spectrofluorimeter at excitation and emission wavelengths of 370 and 440 nm, respectively. The results showed that with the LPPC added, the formation of AGEs was significantly inhibited. The maximum relative inhibitory rate of LPPC on AGEs formation was up to 79.92%±5.21% after heated for 2.5 h at 80℃, while the relative inhibition rate of LPPC reached about 63.37%±4.12% after 30 min at 100℃. Moreover, there was the dose-effect relationship between the concentration of LPPC and its inhibition rate on AGEs formation: the half inhibitory concentration values of LPPC in the simulated food system at 80 and 100℃ were (0.081±0.006) and (0.144±0.009) mg/mL, respectively. After adding metal ions in the model system, the effect of metal ions on AGEs formation was found to depend on the heating time, as well as on the type of metal ion. The addition of 1.0 mg/L Al3+ promoted the formation of AGEs, whereas the addition of 0.1 and 10.0 mg/L Al3+ suppressed the AGEs formation. The 10.0 mg/L Al3+ had the highest inhibition ratio, up to 58.34%±2.93% and 55.92%±2.94% at 80 and 100℃, respectively. After 1 mg/mL LPPC was added, the inhibition ratio of

  17. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  18. New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins

    NARCIS (Netherlands)

    Roshandel, Delnaz; Klein, Ronald; Klein, Barbara E. K.; Wolffenbuttel, Bruce H. R.; van der Klauw, Melanie M.; van Vliet-Ostaptchouk, Jana V.; Atzmon, Gil; Ben-Avraham, Danny; Crandall, Jill P.; Barzilai, Nir; Bull, Shelley B.; Canty, Angelo J.; Hosseini, S. Mohsen; Hiraki, Linda T.; Maynard, John; Sell, David R.; Monnier, Vincent M.; Cleary, Patricia A.; Braffett, Barbara H.; Paterson, Andrew D.

    2016-01-01

    Skin fluorescence (SF) noninvasively measures advanced glycation end products (AGEs) in the skin and is a risk indicator for diabetes complications. N-acetyltransferase 2 (NAT2) is the only known locus influencing SF. We aimed to identify additional genetic loci influencing SF in type 1 diabetes (T1

  19. A New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes also Associated with Blood and Skin Glycated Proteins

    NARCIS (Netherlands)

    Roshandel, Delnaz; Klein, Ronald; Klein, Barbara E K; Wolffenbuttel, Bruce H R; van der Klauw, Melanie M; van Vliet-Ostaptchouk, Jana V; Atzmon, Gil; Ben-Avraham, Danny; Crandall, Jill P; Barzilai, Nir; Bull, Shelley B; Canty, Angelo J; Hosseini, S Mohsen; Hiraki, Linda T; Maynard, John; Sell, David R; Monnier, Vincent M; Cleary, Patricia A; Braffett, Barbara H; Paterson, Andrew D

    2016-01-01

    Skin fluorescence (SF) non-invasively measures advanced glycation end products (AGEs) in the skin and is a risk indicator for diabetic complications. N-acetyltransferase 2 (NAT2) is the only known locus influencing SF. We aimed to identify additional genetic loci influencing SF in type 1 diabetes (T

  20. The inhibitory effect of selenium nanoparticles on protein glycation in vitro

    International Nuclear Information System (INIS)

    Selenium nanoparticles (Se NPs) possess well-known excellent biological activities and low toxicity, and have been employed for numerous applications except as inhibitors to protein glycation. Herein, the present study is carried out to investigate the inhibitory effect of Se NPs on protein glycation in a bovine serum albumin (BSA)/glucose system. By measuring the amount of glucose covalently bound onto BSA, the formation of fructosamine and fluorescent products, it is found that Se NPs can hinder the development of protein glycation in a dose-dependent but time-independent manner under the selected reaction conditions (55 °C, 40 h). And after comparing the increase of inhibitory rate in different stages, it is observed that Se NPs show the greatest inhibitory effect in the early stage, then in the advanced stage, but no effect in the intermediate stage. Fourier transform infrared spectroscopy characterization of Se NPs collected after glycation and determination of ·OH influence and glyoxal formation show that the mechanism for the inhibitory efficacy of Se NPs is related to their strong competitive activity against available amino groups in proteins, their great scavenging activity on reactive oxygen species and their inhibitory effect on α-dicarbonyl compounds’ formation. In addition, it is proved that Se NPs protect proteins from structural modifications in the system and they do not exhibit significant cytotoxicity towards BV-2 and BRL-3A cells at low concentrations (10 and 50 μg mL−1). Consequently, Se NPs may be suitable for further in vivo studies as novel anti-glycation agents. (paper)

  1. Anti-glycation and anti-oxidation properties of Capsicum frutescens and Curcuma longa fruits: possible role in prevention of diabetic complication.

    Science.gov (United States)

    Khan, Ibrar; Ahmad, Haroon; Ahmad, Bashir

    2014-09-01

    The accumulation of advanced glycationend products (AGE's) in the body, due to the non-enzymatic glycation of proteins is associated with several pathological conditions like aging and diabetes mellitus. Hence a plant having anti-glycation and anti-oxidation potentials may serve as therapeutic agent for diabetic complications and aging. In this study the anti-glycation and anti-oxidation properties of crude methanolic extracts of fruits of Capsicum frutescens and Curcuma longa were investigated. Among the two C. frutescens had more anti-glycation ability with a minimum inhibitory concentration (MIC50) of 90βg/mLas compared to 324βg/mL MIC50 of C. longa. Curcuma longa had the more anti-oxidation potential i.e. 35.01, 30.83 and 28.08% at 0.5mg, 0.25mg and 0.125mg respectively.

  2. Multiphoton spectral microscopy for imaging and quantification of tissue glycation

    OpenAIRE

    Tseng, Jo-Ya; Ghazaryan, Ara A.; Lo, Wen; Chen, Yang-Fang; Hovhannisyan, Vladimir; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

    2010-01-01

    Tissue glycation from diabetes and aging can result in complications such as renal failure, blindness, nerve damage and vascular diseases. In this work, we applied multiphoton microscopy for imaging and characterizing the extent of tissue glycation. The characteristic features of multiphoton autofluorescence (MPAF) and second harmonic generation (SHG) images as well as MPAF spectra of glycated bovine skin, cornea and aorta were acquired. The analysis of MPAF intensity change accompanying the ...

  3. Transcapillary escape rate and relative metabolic clearance of glycated and non-glycated albumin in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Bent-Hansen, L; Feldt-Rasmussen, B; Kverneland, A;

    1987-01-01

    -glycated albumin in all groups, but significant only in normal control subjects. No difference in the catabolic rate of glycated and non-glycated albumin was found. We conclude that the in vivo effects of glycation on the clearance and transcapillary passage of albumin are small and not likely to play any...

  4. Plasma disappearance of glycated and non-glycated albumin in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Bent-Hansen, L; Feldt-Rasmussen, B; Kverneland, Arne;

    1993-01-01

    The fractional plasma escape rates of glycated and non-glycated albumin have earlier been measured in groups of Type 1 (insulin-dependent) diabetic patients and control subjects. The escape of non-glycated albumin was similar in control subjects and normoalbuminuric patients, but elevated...... of selectivity (1.002 +/- 0.0068 (SEM), p diabetic microangiopathy. The structural target for these changes is likely...

  5. Serum glycated albumin, but not glycated hemoglobin, is low in relation to glycemia in men with hypertriglyceridemia

    OpenAIRE

    Koga, Masafumi; Murai, Jun; SAITO, HIROSHI; Mukai, Mikio; Kasayama, Soji

    2010-01-01

    Abstract Aims/Introduction:  Serum glycated albumin (GA) and glycated hemoglobin (HbA1c) are influenced by plasma glucose levels, and are used for monitoring chronic glycemic control in diabetic patients. Both glycated proteins are known to be influenced by various factors other than plasma glucose levels. In the present study, we examined the effects of hypertriglyceridemia on them. Materials and Methods:  The present study comprised 273 non‐diabetic men. They were grouped into men with norm...

  6. Use and disposal of end-products (Stabilisa) of spray dryer absorption process

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, G.

    1986-01-01

    The end-products of the spray dryer absorption (SDA) process contain considerable amounts of calcium and sulfur and exhibit hydraulic/pozzolanic properties. These end products can be used for: (1) building materials; (2) cement fabrication; and (3) combined production of sulfuric acid and cement clinker by the Mueller-Kuehne-Process. Before disposal of the SDA end-products, conditioning is necessary, the high compressive strengths and low permeabilities qualify these materials as non-hazardous waste suitable for landfill and land reclamation.

  7. 人巨细胞病毒和糖基化终产物共同作用对血管内皮细胞的影响%Co-effects of human cytomegalovirus infection and advanced glycation end products on vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    李树英; 刘娟; 吴建敏; 周亚滨; 张风雷; 程轶喆; 于晗; 齐眉; 唐伟; 王红

    2007-01-01

    目的:观察人巨细胞病毒(human cytomegalovirus,HCMV)和糖基化终产物(advanced glycation end products, AGEs)共同作用对血管内皮细胞(vein endothelial cells,ECV)氧化应激的影响及对糖基化终产物受体(the receptor for advanced glycation end products, RAGE)表达的影响,明确HCMV和AGEs在致内皮细胞损伤作用中是否具有协同效应,探讨HCMV和AGEs致动脉粥样硬化 (AS)发生和发展的可能机制.方法:用HCMV和AGEs分别及共同作用于ECV,将实验对象分为:对照组、HCMV组、牛血清白蛋白(BSA)组、AGEs组、AGEs+HCMV组5组;用激光共聚焦显微镜检测细胞内活性氧(ROS)的改变;采用RT-PCR方法检测血管内皮细胞RAGEmRNA的表达.结果:HCMV感染ECV后,对照组荧光强度和BSA组荧光强度均较弱,两组间比较差异无统计学意义(P>0.05);AGEs组和HCMV组荧光强度强于对照组(P<0.01);AGEs+HCMV组荧光强度高于AGEs组和HCMV组(P<0.05),两者联合作用存在协同效应.对照组和BSA组ECV细胞RAGEmRNA均有低水平表达,两组之间比较无差异(P>0.05);AGEs组和HCMV感染组RAGEmRNA表达量高于对照组(P<0.01);AGEs+HCMV组表达量高于AGEs组和HCMV组(P<0.01).在相同病毒滴度感染的情况下,随AGEs浓度增加RAGEmRNA的表达增高,呈浓度依赖性;在相同AGEs浓度作用时,随HCMV感染滴度增加RAGEmRNA的表达水平升高,呈滴度依赖性.各组之间比较差异有统计学意义(P<0.05).结论:HCMV和AGEs均能够增强血管内皮细胞氧化应激,促进RAGEmRNA的表达,两者共同作用时呈协同效应.HCMV和AGEs有可能通过协同增强氧化应激、进一步上调RAGEmRNA的表达,介导血管内皮细胞的炎症反应,促进动脉粥样硬化的发生、发展.

  8. Effect of Process Conditions on Advanced Glycation End Product Formation in BSA-Glucose System%加工条件对BSA-Glucose模拟体系中晚期糖基化末端产物形成的影响

    Institute of Scientific and Technical Information of China (English)

    房红娟; 李红姣; 张双凤; 刘荟萃; 李巨秀

    2012-01-01

    This paper reports on the results of an investigation into the effects of temperature,heating time,initial pH,protein concentration and antioxidant type on the formation of advanced glycation end products(AGEs) in a simulated thermal processing system consisting of BSA and glucose.Fluorescence intensity at an excitation/emission wavelength of 370 nm/440 nm was used as a measure of the formation of AGEs.The results showed that the production of AGEs tended to first increase to the maximum at 100 ℃ and 60 min,respectively,and then decrease with increasing temperature and prolonged heating time.Initial pH was an important variable that influences the formation of AGEs;the largest amount of AGEs were formed at pH 7.0,followed by alkaline conditions,and the formation of AGEs was minimized under acid conditions.The formation of AGEs was substantially affected by tea polyphenols,liquorice flavonoids and rosemary acid but little affected by Fe2+,Fe3+,Al3+,Zn2+ or Ca2+.Hence,the formation of AGEs is affected importantly by process conditions including heating time,temperature and initial pH,and is inhibited by tea polyphenols,liquorice flavonoids and rosemary acid as food-grade natural antioxidants but is not affected by metal ions.%建立牛血清白蛋白-葡萄糖(BSA-Glucose)热加工模拟体系,用荧光光谱法测定激发光谱/发射光谱(λex/λem)=370nm/440nm荧光值,研究加热温度、加热时间、初始pH值、蛋白质浓度、抗氧化剂对晚期糖基化末端产物(advanced glycation end products,AGEs)形成的影响。结果表明:随着加热温度升高和加工时间延长,AGEs含量呈现先增加后减少的趋势,分别在100℃、60min时达到最大值;初始pH值对AGEs形成具有重要影响,pH7.0时产生AGEs最多,碱性条件次之,酸性条件最少;茶多酚、迷迭香酸、甘草黄酮对AGEs的生成具有显著的抑制作用;金属离子中Fe3+、Fe2+、Al3+、Zn2+和Ca2+对AGEs的形成无显著影

  9. Effects of advanced glycation end products on the expression of matrix matelloproteinases in human gingival fibroblasts%糖基化终产物对人牙龈成纤维细胞2种基质金属蛋白酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    邓雨泉; 付云; 李华菁

    2012-01-01

    目的 研究糖基化终产物(advanced glycation end products,AGEs)对人牙龈成纤维细胞(human gingival fibroblasts,HGF)表达基质金属蛋白酶-1(matrix matelloproteinase-1,MMP-1)和基质金属蛋白酶-8(matrix matalloproteinase-8,MMP-8)的影响,探讨糖尿病加速牙周炎发展的可能机制.方法 将培养的HGF随机分成6组:空白对照组只加入培养液;阴性对照组仅加入含50 μg/mL人血清白蛋白(human serum albumin,HSA)的培养液;4个含AGE-HSA的实验组分别加入含0.5、5、50、100 μg/mL AGE-HSA的培养液.培养24、48、72 h后,分别应用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)和实时定量聚合酶链反应(real-time quantitative polymerase chain reaction,QPCR)检测细胞MMP-1、MMP-8的蛋白和mRNA表达.结果 100 μg/mL AGE-HSA组培养24、48和72 h后,MMP-1水平明显高于阴性对照组、空白对照组及0.5μg/mL AGE-HSA组,差异具有统计学意义(P<0.05).各浓度AGE-HSA组MMP-1 mRNA水平均显著高于阴性对照组,差异有统计学意义(P<0.05).各浓度AGE-HSA组MMP-8水平与阴性对照组相比差异均无统计学意义(P>0.05),MMP-8 mRNA表达均为阴性.结论 AGEs可能通过促进HGF合成MMP-1,介导胶原降解,从而加重糖尿病患者的牙周组织破坏,尚不能说AGEs影响MMP-8的表达.%Objective To explore the role of advanced glycation end products (AGEs) in modulating the expression of matrix matelloproteinase-1 (MMP-1) and matrix matelloproteinase-8 (MMP-8) in human gingival fibroblasts (HGF). Methods The cultured HGF cells were randomly divided into six groups: blank control group, HSA 50 μg/mL stimulation group (negative control group) and AGE-modified human serum albumin (AGE-HSA) 0.5, 5, 50 and 100 μg/mL stimulation groups. After 24, 48 and 72 hours of culturing, MMP-1 and MMP-8 protein and mRNA expression were detected by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction

  10. Evaluation of a reference material for glycated haemoglobin

    NARCIS (Netherlands)

    Weykamp, CW; Penders, TJ; Muskiet, FAJ; vanderSlik, W

    1996-01-01

    The use of lyophilized blood as a reference material for glycated haemoglobin was investigated with respect to IFCC criteria for calibrators and control materials. Ninety-two laboratories, using 11 methods, detected no changes in glycated haemoglobin content when the lyophilizate was stored for one

  11. Investigation of bovine serum albumin glycation by THz spectroscopy

    Science.gov (United States)

    Cherkasova, Olga P.; Nazarov, Maxim M.; Shkurinov, Alexander P.

    2016-04-01

    Protein glycation is accelerated under hyperglycemic conditions resulting to loss in the structure and biological functions of proteins. The transmission THz spectroscopy has been used for measuring of bovine serum albumin glycation dynamics. It was found that amplitude of albumin THz absorption depends on type of sugars and incubation time.

  12. Moringa oleifera aqueous leaf extract inhibits reducing monosaccharide-induced protein glycation and oxidation of bovine serum albumin.

    Science.gov (United States)

    Nunthanawanich, Pornpimon; Sompong, Weerachat; Sirikwanpong, Sukrit; Mäkynen, Kittana; Adisakwattana, Sirichai; Dahlan, Winai; Ngamukote, Sathaporn

    2016-01-01

    Advanced glycation end products (AGEs) play an important factor for pathophysiology of diabetes and its complications. Moringa oleifera is one of the medicinal plants that have anti-hyperglycemic activity. However, anti-glycation property of Moringa oleifera leaf extract on the different types of reducing monosaccharides-induced protein glycation has not been investigated. Therefore, the aim of this study was to examine the protective effect of Moringa oleifera aqueous leaf extract (MOE) on reducing sugars-induced protein glycation and protein oxidation. Total phenolic content of MOE was measured using the Folin-Ciocalteu method. Bovine serum albumin was incubated with 0.5 M of reducing sugars (glucose or fructose) with or without MOE (0.5-2.0 mg/mL) for 1, 2, 3 and 4 weeks. The results found that total phenolic content was 38.56 ± 1.50 mg gallic acid equivalents/g dry extract. The formation of fluorescent and non-fluorescent AGEs [N (ε)-(carboxymethyl) lysine (CML)] and the level of fructosamine were determined to indicate protein glycation, whereas the level of protein carbonyl content and thiol group were examined for protein oxidation. MOE (0.5-2.0 mg/mL) significantly inhibited the formation of fluorescent, N (ε)-CML and markedly decreased fructosamine level (P < 0.05). Moreover, MOE significantly prevented protein oxidation manifested by reducing protein carbonyl and the depletion of protein thiol in a dose-dependent manner (P < 0.05). Thus, the findings indicated that polyphenols containing in MOE have high potential for decreasing protein glycation and protein oxidation that may delay or prevent AGE-related diabetic complications. PMID:27468399

  13. Moringa oleifera aqueous leaf extract inhibits reducing monosaccharide-induced protein glycation and oxidation of bovine serum albumin.

    Science.gov (United States)

    Nunthanawanich, Pornpimon; Sompong, Weerachat; Sirikwanpong, Sukrit; Mäkynen, Kittana; Adisakwattana, Sirichai; Dahlan, Winai; Ngamukote, Sathaporn

    2016-01-01

    Advanced glycation end products (AGEs) play an important factor for pathophysiology of diabetes and its complications. Moringa oleifera is one of the medicinal plants that have anti-hyperglycemic activity. However, anti-glycation property of Moringa oleifera leaf extract on the different types of reducing monosaccharides-induced protein glycation has not been investigated. Therefore, the aim of this study was to examine the protective effect of Moringa oleifera aqueous leaf extract (MOE) on reducing sugars-induced protein glycation and protein oxidation. Total phenolic content of MOE was measured using the Folin-Ciocalteu method. Bovine serum albumin was incubated with 0.5 M of reducing sugars (glucose or fructose) with or without MOE (0.5-2.0 mg/mL) for 1, 2, 3 and 4 weeks. The results found that total phenolic content was 38.56 ± 1.50 mg gallic acid equivalents/g dry extract. The formation of fluorescent and non-fluorescent AGEs [N (ε)-(carboxymethyl) lysine (CML)] and the level of fructosamine were determined to indicate protein glycation, whereas the level of protein carbonyl content and thiol group were examined for protein oxidation. MOE (0.5-2.0 mg/mL) significantly inhibited the formation of fluorescent, N (ε)-CML and markedly decreased fructosamine level (P < 0.05). Moreover, MOE significantly prevented protein oxidation manifested by reducing protein carbonyl and the depletion of protein thiol in a dose-dependent manner (P < 0.05). Thus, the findings indicated that polyphenols containing in MOE have high potential for decreasing protein glycation and protein oxidation that may delay or prevent AGE-related diabetic complications.

  14. Correlation of the expressions of advanced glycation end products and its receptor in serum and ;placenta with the pathogenesis of preeclampsia%孕妇血清及胎盘组织中晚期糖基化终末产物及其受体的表达水平变化与子痫前期发病的相关性

    Institute of Scientific and Technical Information of China (English)

    仙娜; 陈维萍; 张妍; 李静; 张宁; 叶元华

    2015-01-01

    Objective To investigate the correlation of the expressions of advanced glycation end products(AGE) and the receptor for advanced glycation end products(RAGE) in serum and placenta with the pathogenesis of preeclampsia. Methods From December 2013 to June 2014, 32 women with severe preeclampsia who received cesarean section in the Affiliated Hospital of Qingdao University were recruited in the study, defined as the severe preeclampsia group. 30 healthy pregnant women who received cesarean section in the same hospital were recruited as the control group. ELISA was used to measure the maternal serum AGE, soluble receptor for advanced glycation end products (sRAGE) and tumor necrosis factor-α(TNF-α) in these women. Furthermore, ELISA was also used to measure AGE and TNF-α in the placenta. The localizations of AGE and RAGE protein in placentas were detected by immunohistochemical SP method. RAGE and TNF-α mRNA expression in placentas were measured by real-time quantitative PCR. AGE, RAGE and TNF-αprotein expression in placentas were measured by western blot, respectively. Results (1) The serum levels of AGE,sRAGE and TNF-αin the severe preeclampsia group were (538 ± 75),(367 ± 86) and (322 ± 40) ng/L,respectively. They were significantly higher than those in the control group[(454 ± 50), (286 ± 35) and (270 ± 35) ng/L, respectively](P0.05). (2) In the severe preeclampsia group, the levels of AGE and TNF-αin placentas were (500 ± 82) and (334 ± 57) ng/L, which were higher than those in the control group [(431 ± 74) and (263 ± 46) ng/L, respectively](P0.05)。(2)重度子痫前期组胎盘组织中AGE及TNF-α水平分别为(500±82)及(334±57)ng/L,明显高于健康对照组的(431±74)及(263±46)ng/L,两组分别比较,差异均有统计学意义(P<0.05)。重度子痫前期组孕妇胎盘组织中AGE水平与TNF-α水平呈显著正相关(r=0.406,P<0.05)。(3)重度子痫前期组及健康对照组胎盘组

  15. Nonenzymatic glycation of phosphatidylethanolamine in erythrocyte vesicles

    International Nuclear Information System (INIS)

    Unsealed inside-out and right-side out vesicles were prepared from human red cells. The vesicles were incubated with D-glucose [14C(U)] and sodium cyanoborohydride in phosphate buffer, pH 7.4. After incubation, lipids were extracted with 1-butanol and non-lipid contaminants removed by Sephadex G-25 chromatography. Phosphatidylethanolamine-sorbitol was purified by chromatography on columns of silicic acid and phenylboronate agarose gel. Phospholipase C (B. cereus) liberated phosphoethanolamine-sorbitol (I) which comigrated on TLC with synthetic I prepared by reductive condensation of phosphoethanolamine and D-glucose and also with the product of phospholipase C (B. cereus) hydrolysis of reference phosphatidylethanolamine-sorbitol. Exposure of I to alkaline phosphatase (E. coli) gave P/sub i/ and ethanolamine-sorbitol (II) which comigrated on TLC with synthetic II prepared by reductive condensation of ethanolamine and D-glucose or by phospholipase D hydrolysis of reference phosphatidylethanolamine-sorbitol. These studies demonstrate that vesicular phosphatidylethanolamine can be reductively glycated and illustrate the applicability of both phospholipase C and phospholipase D in characterizing glycated phosphoglycerides

  16. Effect of Advanced Glycation End Products on Expression of Urotensin Ⅱ and G-Protein-Couple Receptor mRNAs in Rat Mesangial Cells%糖基化终末产物对大鼠肾小球系膜细胞尾加压素Ⅱ及G蛋白偶联受体mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵岩; 林风武; 李才

    2010-01-01

    目的 观察不同浓度糖基化终末产物(Advanced glycation end products,AGEs)及AGEs作用不同时间对大鼠肾小球系膜细胞尾加压素Ⅱ(UrotensinⅡ,UⅡ)及G蛋白偶联受体(G-protein-couple receptor,GPR14)mRNA表达的影响.方法 制备AGE-BSA,体外培养大鼠肾小球系膜细胞(Mesangial cells,MC),加入不同浓度的AGE-BSA(终浓度分别为0、25、50、100和200 mg/L),37℃孵育24 h;加入100 mg/L AGE-BSA,分别培养0、2、8、16和24 h,以不含葡萄糖的BSA作为对照.收集细胞,采用RT-PCR检测各组MC UⅡ及GPR14 mRNA的表达.结果 AGE-BSA各组MC UⅡ及GPR14 mRNA的表达量均随AGEs浓度的增加而增加,50、100和200 mg/L与0 mg/L组比较,差异有统计学意义(P<0.05);100 mg/L AGE-BSA各组MC UⅡ及GPR14 mRNA的表达量随着作用时间的延长而增加,作用8、16、24 h组与0 h组比较,差异有统计学意义(P<0.05).BSA组MC UⅡ及GPR14 mRNA的表达量无明显增加(P>0.05).结论 AGEs能上调大鼠MC UⅡ及GPR14 mRNA的表达.

  17. Relationship between the advanced glycation end products content and expressions of RAGE,ICAM-1 in vascular tissue of diabetic rats%糖尿病大鼠血管糖基化终产物含量与其受体和ICAM-1表达的关系

    Institute of Scientific and Technical Information of China (English)

    张建伟; 孙仁宇

    2001-01-01

    In this study,the relationship between the advanced glycation end products(AGEs) and the expressions of receptor for AGEs(RAGE),intercellular cell adhesion molecule-1(ICAM-1) was investigated.The diabetic rat model was reconstructed and the fluorescence method,RT-PCR and in-situ hybridization techniques were used to detect AGEs content and the expressions of RAGE and ICAM-1 gene in the aorta and cardiac tissues.The results showed that AGEs content in aortic and cardiac tissues increased(P<0.01) in diabetic rats; The expressions of RAGE and ICAM-1 enhanced (P<0.05~0.01) and were positively correlated with the quantity of AGEs accumulation(P<0.01) in the aorta and cardiac tissue.These parameters change in the diabetic rats can be improved with aminoglumine(AG) treatment.Suggesting that AGEs might induce RAGE and ICAM-1 expression.It's postulated that AGEs binding to RAGE play an important role to result in diabetic endothelial cells dysfunction and lesion.%探讨糖尿病大鼠血管组织糖基化终产物(AGEs)含量与其受体(RAGE)和细胞间粘附因子-1(ICAM-1)表达的关系。复制糖尿病大鼠模型,采用荧光法、RT-PCR及原位杂交方法检测主动脉及心肌组织的AGEs含量以及RAGE和ICAM-1基因的表达。发现糖尿病大鼠主动脉和心肌组织AGEs含量升高(P<0.01);RAGE和ICAM-1基因表达增强(P<0.05~0.01);AGEs含量与RAGE及ICAM-1呈明显正相关(P<0.01);氨基胍治疗可缓解上述指标的变化。提示AGEs可诱导RAGE和ICAM-1的表达。推测AGEs -RAGE相互作用是引起糖尿病血管内皮细胞功能紊乱和损伤的关键环节。

  18. Water Extraction of Cinnamon Proanthocyanidins and Its Inhibitory Effect on the Formation of Advanced Glycation End Products%肉桂原花青素的提取及其对高级糖基化终产物形成的抑制作用

    Institute of Scientific and Technical Information of China (English)

    黎超; 毛超伦; 雍克岚

    2012-01-01

    One factor-at-a-time and orthogonal array design methods were used to determine the optimal operating conditions for water extraction of proanthocyanidins from cinnamon(CPAs).Nine types of macroporous adsorption resin were compared for their effectiveness in adsorbing and desorbing CPAs.Meanwhile,the in vitro inhibitory effect of CPAs on the formation of advanced glycation end products(AGEs) was tested.The optimal extraction conditions were found to be 2 h of extraction at 60 ℃ with acidic water at pH 5.0(adjusted with sodium acetate-acetic acid buffe) at a liquid/solid ratio of 14:1(mL/g).Under these conditions,the extraction rate of CPAs was 14.27 mg/g.LSA-21 resin was the most effective in purifying CPAs.CPAs had strong inhibitory activity on the formation of AGEs with an IC50 of 45.93μg/mL,which was higher than that of the positive control aminoguanidimine.%通过单因素和正交试验确定肉桂中原花青素(proanthocyanidins of cinnamon,CPAs)最佳水提工艺条件,比较9种大孔吸附树脂对CPAs的吸附与解吸性能,对CPAs进行体外蛋白非酶糖化抑制实验。结果表明:最佳提取条件为液料比14:1(mL/g)、提取温度60℃、pH5.0、提取时间2h,CPAs提取得率为14.27mg/g,LSA-21大孔吸附树脂分离纯化CPAs效果最佳。该肉桂提取物对高级糖基化终产物的形成具有很好的抑制活性,其IC50为45.93μg/mL,高于阳性对照氨基胍。

  19. Characterization of Clostridium thermocellum strains with disrupted fermentation end-product pathways

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Veen, Douwe [ORNL; Lo, Jonathan [Dartmouth College; Brown, Steven D [ORNL; Johnson, Courtney M [ORNL; Tschaplinski, Timothy J [ORNL; Martin, Madhavi Z [ORNL; Engle, Nancy L [ORNL; Van den Berg, Robert A [Katholieke University Leuven, Belgium; Argyros, Aaron [Mascoma Corporation; Caiazza, Nicky [Mascoma Corporation; Guss, Adam M [ORNL; Lynd, Lee R [Thayer School of Engineering at Dartmouth

    2013-01-01

    Clostridium thermocellum is a thermophilic, cellulolytic anaerobe that is a candidate microorganism for industrial biofuels production. Strains with mutations in genes associated with production of L-lactate (Dldh) and/or acetate (Dpta) were characterized to gain insight into the intracellular processes that convert cellobiose to ethanol and other fermentation end-products. Cellobiose-grown cultures of the Dldh strain had identical biomass accumulation, fermentation end-products, transcription profile, and intracellular metabolite concentrations compared to its parent strain (DSM1313 Dhpt Dspo0A). The Dpta-deficient strain grew slower and had 30 % lower final biomass concentration compared to the parent strain, yet produced 75% more ethanol. A Dldh Dpta double-mutant strain evolved for faster growth had a growth rate and ethanol yield comparable to the parent strain, whereas its biomass accumulation was comparable to Dpta. Free amino acids were secreted by all examined strains, with both Dpta strains secreting higher amounts of alanine, valine, isoleucine, proline, glutamine, and threonine. Valine concentration for Dldh Dpta reached 5 mM by the end of growth, or 2.7 % of the substrate carbon utilized. These secreted amino acid concentrations correlate with increased intracellular pyruvate concentrations, up to sixfold in the Dpta and 16-fold in the Dldh Dpta strain. We hypothesize that the deletions in fermentation end-product pathways result in an intracellular redox imbalance, which the organism attempts to relieve, in part by recycling NADP* through increased production of amino acids.

  20. 糖基化终末产物促SH-SY5Y细胞β-淀粉样蛋白生成及相关机制%Effect of advanced glycation end products on expression of the β-amyloid protein in SH-SY5Y cells and its related mechanism

    Institute of Scientific and Technical Information of China (English)

    徐松; 高顺宗; 刘雪平; 王美霞; 董传芳; 侯亮; 袁树华

    2011-01-01

    目的 通过研究糖基化终末产物(AGEs-BSA)对培养的人神经母细胞瘤细胞(SH-SY5Y细胞)β-淀粉样蛋白(Aβ)的生成,以及淀粉样前体蛋白(APP)及相关酶-β-分泌酶(BACEl)、γ-分泌酶(PS1)的表达的影响,在体外水平探讨AGEs-BSA在阿尔茨海默病(AD)发病中的作用及其可能的机制.方法 以培养的SH-SY5Y细胞为模型,将细胞随机分为4组.用MTT实验得到的AGEs-BSA最佳干预时间及浓度干预细胞,用免疫细胞化学方法及ELISA方法观察及检测各组细胞内Aβ1-40、Aβ1-42表达,用免疫印迹法检测各组细胞内APP、BACE1、PS1变化.结果 BSA组与空白对照组相比APP、BACE1、PS1、Aβ的表达无明显差异(P>0.05);AGEs-BSA组与BSA组相比APP、BACE1、PS1、Aβ的表达明显增加(P<0.05);AGEs-BSA+抗RAGE中和抗体组APP、BACE1、PS1、Aβ的表达较单纯AGEs-BSA组明显减少(P<0.05),但仍高于BSA组(P<0.05).结论 糖基化终末产物能够促使SH-SY5Y细胞中APP的表达增加,并通过上调BACE1、PS1的活性使Aβ生成增加.通过阻断其与特异性受体RAGE的结合可以部分减少APP、BACE1,PS1及Aβ的表达和生成.%Objective To investigate the effect of advanced glycation end products (AGEs) on expressions of the β-amyloid protein (Aβ) and its related enzymes in cultured SH-SY5Y cells, and explore the effect and possible mechanism of AGEs on Alzheimer's disease(AD) the cell level.Methods Cultured SH-SY5Y cells were randomly divided into four groups: the blank control group, the AGE-modified bovine serum albumin (AGEs-BSA) group, the AGEs-BSA + anti-receptor for advanced glycation end products(RAGE) group and the BSA group.The MTT metabolic rate was employed to determine cells' growth and best concentration and time of the AGEs-BSA.Immunocytochemistry and ELISA were used to observe expressions of Aβ1-40 and Aβ1-42.Western blot was employed to examine changes of the amyloid precursor protein ( APP), β- secretion enzymel

  1. Injury effects of advanced glycation end products on the cultured primary rat basal forebrain cholinergic neurons%糖基化终末产物对大鼠基底前脑胆碱能神经元的损伤作用

    Institute of Scientific and Technical Information of China (English)

    殷青青; 刘雪平; 董传芳; 董雪丽; 李艳菊; 罗鼎真; 侯训尧

    2012-01-01

    目的 研究糖基化终末产物(AGE-BSA)对原代培养的基底前脑胆碱能神经元形态、生存率、凋亡率、胆碱乙酰转移酶(ChAT)与乙酰胆碱酯酶(AchE)活性的影响.在体外水平研究AGEs在阿尔茨海默病(Alzheimer's disease,AD)神经元缺失发生中的作用及其可能机制.方法 原代培养大鼠基底前脑胆碱能神经元,观察细胞生长变化,进行免疫荧光细胞化学鉴定;用300 μg/mLAGE-BSA以及糖基化终末产物受体(RAGE)中和抗体阻断处理原代培养的基底前脑胆碱能神经元,作用不同时间后置于倒置显微镜下观察细胞形态变化;采用MTT法检测神经元的存活率;采用流式细胞术检测神经元的凋亡率;经比色法检测ChAT和AchE的活性变化.结果 AGEBSA干预胆碱能神经元72 h后,细胞形态发生明显损伤性变化,细胞存活率明显降低,凋亡率增高,ChAT活性明显下降,AchE活性明显升高;RAGE中和抗体阻断组72 h较之AGE-BSA组,细胞形态损伤变化较轻,生存率偏高,凋亡率较低,ChAT活性较高,AchE活性偏低,但比空白对照组生存率降低,凋亡率增高,ChAT活性明显下降,AchE活性明显升高.结论 糖基化终末产物作用72 h可以引起胆碱能神经元的损伤,并造成ChAT活性下降和AchE活性明显升高,部分阻断其与特异性受体RAGE的结合可以减弱其损伤作用,提示糖基化终末产物通过其受体参与了对胆碱能神经元的损伤作用.%Objective To investigate effects of advanced glycation end products (AGEs) on the cell morphology, survival rate, apoptosis rate, choline acetyltransfesterase (ChAT) activity and acetylcholine( AchE) activity of the cultured primary rat basal forebrain cholinergic neurons. To explore the effect and the possible mechanism of AGEs in Alzheimer's disease( AD) at the cell level. Methods Cultured primary rat basal forebrain cholinergic neurons were intervened by AGE-BSA and the RAGE neutralizing antibody, then the cell

  2. RAGE阻断剂FPS-ZM1对糖基化终末产物所致大鼠脑部炎症反应的影响及机制%Effects of RAGE inhibitor FPS-ZM1 on inflammatory reaction in the brain of rats induced by advanced glycation end products

    Institute of Scientific and Technical Information of China (English)

    孙梦晗; 洪艳; 候训尧; 马莹娟; 申超; 罗鼎真; 刘雪平

    2014-01-01

    目的:探讨RAGE受体特异性阻断剂FPS-ZM1对糖基化终末产物( AGEs)所致大鼠脑部炎症反应及认知功能的影响。方法将40只大鼠随机分为四组:生理盐水组( NC组) FPS-ZM1对照组、AGEs组和FPS-ZM1组,采用脑立体定位技术,向AGEs组及FPS-ZM1组大鼠两侧海马注射AGEs 5μl,以制造动物损伤模型,用同样方法向 NC组及 FPS-ZM1对照组注射等量生理盐水,以制造模型对照;造模前1 w以1 mg · kg-1· d-1 FPS-ZM1向FPS-ZM1组和FPS-ZM1对照组大鼠进行腹腔注射,并连续4 w给药,AGEs组、NC组则同时注射相同体积生理盐水,造模3 w后对各组大鼠进行Morris水迷宫实验,检测各组大鼠逃逸潜伏期( EL);用 Elisa 检测各组大鼠海马区 Aβ1~40, Aβ1~42的水平;用 Western 印迹检测各组大鼠RAGE,p-NF-κB和肿瘤坏死因子( TNF)-α蛋白的表达;用免疫组织化学法检测各组大鼠海马区TNF-α蛋白的表达强度。结果 AGEs组与其他各组相比,EL显著延长(P<0.01),且 Aβ1~40、Aβ1~42浓度均显著升高(P<0.01);同时 AGEs 组 RAGE、p-NF-κB 和 TNF-α的蛋白表达明显增强(P<0.01);FPS-ZM1干预后上述各指标均明显低于AGEs组。结论 FPS-ZM1作为RAGE受体特异性阻断剂,能作用中枢系统减少Aβ1~40,生成从而提高AGEs脑损伤大鼠的智能,并通过抑制脑组织 p-NF-κB上调,减轻脑AGEs损伤引起的炎性反应。该药因能透过血脑屏障有望成为抑制阿尔茨海默样病变的有效措施。%Objective To explore the effects of RAGE inhibitor FPS-ZM1 on inhibiting inflammatory reaction in the brain of rats and cognition induced by advanced glycation end products.Methods Fourty Wistar rats were randomly divided into normal control ( NC) , FPS-ZM1 control , AGEs and FPS-ZM1 groups.By brain stereotactic techniques , the bilateral hippocampus of rats in AGEs group and FPS-ZM1 group were injected

  3. 西红花酸对晚期糖化终产物诱导内皮细胞晚期糖基化终产物受体表达的抑制作用%Crocetin reduces expression of receptor for advanced glycation end products (RAGE) on endothelial cells induced by AGE

    Institute of Scientific and Technical Information of China (English)

    向敏; 钱之玉; 周成华

    2008-01-01

    AIM:To investigate the effects of crocetin on receptor for advanced glycation end products(RAGE) mRNA expression in bovine endothelial cells(BEC) induced by advanced glycation end products(AGE) and the possible mechanisms involved. METHODS:The BEC were preincubated with crocetin(1,0.1 and 0.01 μmol/L) for 12 h,then exposed to AGE (100 mg/L). The RAGE mRNA expression was detected by RT-PCR analysis, the intercellular adhesion molecule-1(ICAM-1) was measured by ELISA. The extracellular superoxide ion and thiobarbituric acid reactive substances (TBARS) were assessed with superoxide ion kit and colorimetric assay, respectively. The intracellular H2O2 was also detected using the probe 2,7-dichlorofluorescein (DCFH). The mitochondrial membrane potential(MMP) and mitochodrial Succinate dehydrogenase(MSDH) were analyzed by the retention of rhodamine123 (Rh123) and MTT. RESULTS:Compared with AGE Group, crocetin was able to significantly reduce RAGE mRNA expression (P<0.05), decrease the content of super anion and TBARS in supernatant media (P<0.01 or P<0.05) and H2O2 in cells (P<0.05). Spontaneously, the MMP and the activity of MSDH were improved. Furthermore, the expression of ICAM-1 protein was suppressed by crocetin in a time-and dose-dependant manner. CONCLUSION:These results demonstrated that crocetin could inhibit RAGE over-expression in AGE-exposed BEC by suppressing the generation of reactive oxygen species active oxygen(ROS). This study suggested that crocetin might have beneficial effects in the treatment of diabetic vascular complications.%目的:研究西红花酸对晚期糖基化终产物(AGE)诱导牛内皮细胞(BEC)中晚期糖基化终产物受体(RAGE)mRNA表达的抑制作用,并探讨其可能机制.方法:不同浓度的西红花酸(1、0.1、0.01 μmol/L)预孵BEC细胞 12 h 后,用AGE(100 mg/L)刺激细胞 12 h, RT-PCR法测定RAGE mRNA的表达水平;ELISA法测定细胞间黏附分子-1(ICAM-1)的表达;试剂盒分别检测胞外超氧阴离子

  4. Targeted reduction of advanced glycation improves renal function in obesity

    DEFF Research Database (Denmark)

    Harcourt, Brooke E; Sourris, Karly C; Coughlan, Melinda T;

    2011-01-01

    if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26-39¿kg/m(2)) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal......-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile...

  5. 自噬在晚期糖基化终产物诱导的内皮细胞凋亡中的作用%Autophagy plays a protective role in advanced glycation end product-induced apoptosis of vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    胡鹏飞; 赖东武; 何红

    2012-01-01

    目的:研究晚期糖基化终产物(AGEs)对人脐静脉内皮细胞(HUVECs)自噬水平的影响并探讨自噬在AGEs诱导的内皮细胞凋亡中的作用.方法:用AGEs处理HUVECs,相同条件牛血清白蛋白处理为对照组,Western blotting检测相应蛋白表达的变化,电镜观察细胞自噬体的出现,流式细胞术检测细胞凋亡,MTT比色法测定细胞活性.结果:AGEs处理HUVECs后,自噬相关蛋白LC3-II的表达显著上调并呈时间和浓度依赖性,电镜观察到细胞胞浆内自噬体数量增加;与对照组比较,AGEs处理组内皮细胞凋亡率增加,活性下降,自噬抑制剂3-甲基腺嘌呤预处理的AGEs组细胞活性较AGEs组进一步下降,凋亡率继续增加.AGEs处理HUVECs后,蛋白激酶B(Akt)和哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化水平也明显下调,Akt激活剂胰岛素样生长因子1预处理后,Akt的磷酸化水平增加,自噬相关蛋白LC3-II的增高表达被抑制.结论:AGEs通过PI3K/Akt/mTOR介导的信号通路诱导HUVECs自噬水平升高.自噬在AGEs诱导的内皮细胞凋亡中对细胞起保护作用.%AIM; To invesligale the effect of advanced glycation end products ( AGEs) on autophagy in human umbilical endolhelial cells (HUVECs) and Lo idenlify the role of aulophagy in advanced glycalion end producl - induced cell apoplosis. METHODS: HUVECs were cullured and Irealed wilh AGEs or bovine serum albumin. The prolein expression was delecled by Weslern blolling. Aulophagosomes were observed under electron microscope. The cell apoplolic rale was delermined by flow cylomelry. The cell viability was quanlified by MTT assay. RESULTS: After trealed wilh AGEs, the level of aulophagy - associated prolein LC3 - II in HUVECs was up - regulated, and the number of aulophagosomes was increased. Compared wilh conlrol group, the apoplolic rale of HUVECs increased and the viability of HUVECs was decreased in AGEs treatmenl group. Furthermore, prelreating the cells with an aulophagy

  6. Productos finales de la glicación y de la lipoxidación como amplificadores de la inflamación: papel de los alimentos Advanced glycation and lipoxidation end products-amplifiers of inflammation: the role of food

    Directory of Open Access Journals (Sweden)

    S. Bengmark

    2007-12-01

    associated with changes in lifestyle habits, including those related to the consumption of processed foodstuffs. In these foods advanced glycation end products (AGE and advanced lipoperoxydation products (ALE are formed as a consequence of the reactivity of proteins, carbohydrates, lipid and other components. The aim of the present review is to offer a perspective of how AGE and ALE affect the physiology and development of CD. Continous intake of AGE and ALE contributes to the exccesive accumulation of these products into body tissues, which in turn negatively influence the innate immune system, inflammatory responses, and resistance to diseases. This is achieved by direct interaction of AGE and ALE with specific cell AGE receptors (RAGE that have a key role as master switches regulating the development of CD. Long-life molecules, namely collagen and myelin, and low-turnover tissues, e.g. connective, bone and neural tissues, are the main targets of AGE and ALE. In these tissues, AGE and ALE lead to the synthesis of insoluble compounds that severely alter cellular functionality. It has been reported associations of AGE and ALE with allergic and autoimmune diseases, Alzheimer disease and other degenerative disorders, catarats, atherosclerosis, cancer, and diabetes mellitus type 2, as well as a number of endocrine, gastrointestinal, skeleton-muscle, and urogenital alterations. Controlling all those pathologies would need further dietary recommendations aiming to limit the intake of processed foods rich in AGE and ALE, as well as to reduce the formation of those products by improving technological processes applicable to foods.

  7. Proteomic Profiling of Nonenzymatically Glycated Proteins in Human Plasma and Erythrocyte Membrane

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Tang, Ning; Schepmoes, Athena A.; Phillips, Lawrence S.; Smith, Richard D.; Metz, Thomas O.

    2008-05-01

    Non-enzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the development of diabetic complications. In this report, a thorough proteomic profiling of glycated proteins was attempted by using phenylboronate affinity chromatography to enrich glycated proteins and glycated, tryptic peptides from human plasma and erythrocyte membranes. Enriched peptides were subsequently analyzed by liquid chromatography coupled with electron transfer dissociation tandem mass spectrometry, and 76 and 31 proteins were confidently identified as glycated from human plasma and erythrocyte membrane, respectively. It was observed that most of the glycated proteins can be identified in samples from individuals with normal glucose tolerance, although samples from individuals with impaired glucose tolerance and type 2 diabetes mellitus have slightly higher numbers of glycated proteins and more glycation sites identified.

  8. Glycation of extracellular matrix proteins impairs migration of immune cells.

    Science.gov (United States)

    Haucke, Elisa; Navarrete-Santos, Alexander; Simm, Andreas; Silber, Rolf-Edgar; Hofmann, Britt

    2014-01-01

    The immune response during aging and diabetes is disturbed and may be due to the altered migration of immune cells in an aged tissue. Our study should prove the hypothesis that age and diabetes-related advanced glycation end products (AGEs) have an impact on the migration and adhesion of human T-cells. To achieve our purpose, we used in vitro AGE-modified proteins (soluble albumin and fibronectin [FN]), as well as human collagen obtained from bypass graft. A Boyden chamber was used to study cell migration. Migrated Jurkat T-cells were analyzed by flow cytometry and cell adhesion by crystal violet staining. Actin polymerization was determined by phalloidin-Alexa-fluor 488-labeled antibody and fluorescence microscopy. We found that significantly fewer cells (50%, p = 0.003) migrated through methylglyoxal modified FN. The attachment to FN in the presence of AGE-bovine serum albumin (BSA) was also reduced (p < 0.05). In ex vivo experiments, isolated collagen from human vein graft material negatively affected the migration of the cells depending on the grade of AGE modification of the collagen. Collagen with a low AGE level reduced the cell migration by 30%, and collagen with a high AGE level by 60%. Interaction of the cells with an AGE-modified matrix, but not with soluble AGEs like BSA-AGE per se, was responsible for a disturbed migration. The reduced migration was accompanied by an impaired actin polymerization. We conclude that AGEs-modified matrix protein inhibits cell migration and adhesion of Jurkat T-cells.

  9. 糖基化终产物对小胶质细胞分泌IL-1β和TNF-α的影响%Effect of advanced glycation end products on interleukin- 1β and tumor necrosis factor α secretion from microglial cells

    Institute of Scientific and Technical Information of China (English)

    王美霞; 刘雪平; 徐松; 董传芳; 侯亮; 袁树华

    2011-01-01

    Objective To research the effect of advanced glycation end products (AGEs) on the levels of interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α)in primary rat microglial cells, and to further explore the effect of AGEs-BSA on Alzheimer's disease(AD) and the possible mechanism at the cell ular level. Methods Cultured microglial cells were intervened by AGEs-BSA and then identified with the immunocytochemistry method, and morphological changes of the cells were observed. After primary rat microglial cells were treated with 300 μg/mL of AGEs-BSA and the RAGE neutralizing antibody, the levels of IL-1 β and TNF-α extracted from the supernatant liquid of microglia were measured by enzyme-linked immunosobent assay (ELISA). Results After the intervention of AGEs-BSA, the cell body became bigger and the shape showed as an “Ameba”, and the levels of IL-1β and TNF-α were significantly increased( P <0. 001 ). Compared with the AGEs-BSA group, the levels of IL-1 β and TNF-α were lower in cells exposed to the RAGE neutralizing antibody before treatment with AGEs-BSA (P <0.01 ), while they were higher than those in the normal control group( P < 0.01 ). Conclusion AGEs-BSA could activate microglia and induce the release of IL-1β and TNF-α in a time-dependent manner, which suggested that AGEs act directly or through the receptor activated microglia-mediated immune inflammatory responses.%目的 研究糖基化终产物(AGEs-BSA)对原代培养的小胶质细胞分泌白细胞介素113(IL-1β)和肿瘤坏死因子α(TNF-α)的影响,在细胞水平探讨AGEs-BSA在阿尔茨海默病(AD)发生中的作用及其可能机制.方法 体外培养小胶质细胞,用AGEs.BSA干预,用免疫细胞化学方法,进行鉴定并观察其形态变化;用AGEs-BSA300μg/mL激活和抗RAGE中和抗体阻断的方法对原代培养的小胶质细胞进行处理,用酶联免疫吸附法(ELISA)检测细胞上清液中IL-lβ和TNF-α的水平.结果 AGEs-BSA干预后小胶

  10. Activation of astrocytes by advanced glycation end products: cytokines induction and nitric oxide release%晚期糖基化终产物诱导星型胶质细胞活化:细胞因子分泌与一氧化氮释放

    Institute of Scientific and Technical Information of China (English)

    王真; 李电东; 梁云燕; 王代树; 蔡年生

    2002-01-01

    目的:研究两种体外温育的晚期糖基化终产物(AGE)是否可以诱导星型胶质细胞分泌白介素-1β和肿瘤坏死因子α,并导致氧应激增加、一氧化氮释放.方法:RT-PCR技术检测两种细胞因子水平及AGE受体(RAGE)存在与否;DTNB反应测量还原型谷胱甘肽的水平:利用Griess试剂测量一氧化氮含量.结果:AGE 1 g/L(尤其是半乳糖温育产物)作用72小时后使星型胶质细胞培养上清和细胞裂解物的细胞因子含量显著升高.且呈剂量依赖性.半定量RT-PCR证明两种细胞因子的变化是由于其转录水平增加所致.AGE还可导致星型胶质细胞内还原性谷胱甘肽减少,一氧化氮释放.RAGE存在于此类星型胶质细胞中.结论:AGE可诱导星型胶质细胞分泌炎性因子白介素-1β和肿瘤坏死因子α,并升高氧应激水平,这至少部分解释了AGE在神经变性性疾病如阿尔采默病和帕金森氏病以及脑衰老中的负性作用.%AIM: To investigate whether two kinds of in vitro prepared advanced glycation end products (AGE), Glu-BSA andGal-BSA, could induce proinflammatory mediators IL-1β and TNF-α, as well as oxidative stress and nitric oxide(NO), in astrocytes, thus contributing to brain injury. METHODS: Radioimmunoassay and RT-PCR techniquewere used to detect two cytokines' level and existence of receptor for AGE (RAGE). DTNB reaction was used tomeasure reduced glutathione (GSH) level. NO content was assayed using Griess reagent provided by Promega.RESULTS: Enhanced protein levels of both cytokines in supernatants and cell lysates of astroglia cultures weredetected after treated with AGE-BSA 1 g/L, especially Gal-BSA, for 72 h. The increases were also in a concentra-tion-dependent manner. Changes in protein levels might be attributed to changes in transcriptional levels docu-mented by semi-quantitative RT-PCR. Both AGE-BSA could also reduce astrocytic GSH and induce NO release.RAGE was detected in astrocytes. CONCLUSION

  11. 阿托伐他汀对2型糖尿病鼠主动脉糖基化终末产物受体基因表达的影响%Effects of atorvastatin on expression of receptor for advanced glycation end products in aorta of type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    冯波; 李栩; 徐雷; 王华; 颜新凤; 薛俊丽

    2011-01-01

    目的 观察阿托伐他汀对2型糖尿病(GK)大鼠动脉壁糖基化终末产物受体(RAGE)基因表达的影响,探讨阿托伐他汀抗糖尿病动脉粥样硬化作用的潜在机制.方法 健康雄性Wistar大鼠5只作为正常对照组,GK大鼠随机分为糖尿病对照组(5只)和糖尿病阿托伐他汀治疗组(4只,每日1次阿托伐他汀20 mg/kg灌胃).各组均采用高脂饮食喂养.12周后,采用透射电镜观察主动脉壁超微结构,定量RT-PCR测定主动脉RAGE和单核细胞趋化蛋白-1(MCP-1)的表达.结果 与正常对照组比较,糖尿病对照组主动脉RAGE和MCP-1表达明显升高,而阿托伐他汀治疗能够降低RAGE和MCP-1的表达.主动脉RAGE表达水平与MCP-1表达水平呈显著正相关(r=0.482,P=0.031).透射电镜下糖尿病大鼠动脉可见超微结构的改变.结论 RAGE表达在2型糖尿病早期动脉粥样硬化形成过程中明显上调,阿托伐他汀可通过下调RAGE的表达抗动脉粥样硬化的形成.%Objective To investigate the effect of atorvastatin on expression of receptor for advanced glycation end products (RAGE) in the aorta of type 2 diabetic Goto-Kakisaki (GK) rats and to discuss the potential anti-atherosclerosis mechanisms of atorvastatin. Methods 5 healthy Wistar rats (normal control group) and 9 GK rats were randomly divided into two groups : diabetic control group and atorvastatin-treated diabetic group (20 mg/kg,qd) were fed with the high fat diet for 12 weeks. The expressions of RAGE mRNA and MCP-1 mRNA of aorta were detected using RT-PCR. Ultramicrostructure of aorta was observed using electron microscope. Results Compared with normal control group , the expressions of RAGE mRNA and MCP-1 mRNA in diabetic control group were significant increased . Decreases in the expressions of RAGE mRNA and MCP-1 mRNA were observed in atorvastatin -treated diabetic group compared with diabetic control group. There was significant correlation between the expression levels of RAGE m

  12. Effects of Ganoderma lucidum polysaccharides on advanced glycation end products and receptor of aorta pectoralis in T2DM rats%灵芝多糖对2型糖尿病大鼠胸主动脉AGEs及其受体的影响

    Institute of Scientific and Technical Information of China (English)

    陈杨; 乔进; 罗佳; 吴锋; 孟国梁; 陈惠; 郑惠华; 徐济良

    2011-01-01

    Objective: To investigate the effects of Ganoderma lucidum polysaccharides(GLPs) on advanced glycation end products(AGEs) and the receptor ( RAGE)of aorta pectoralis in the T2DM rats, and explore the protective mechanism of GLPs on the aorta pectoralis.Method: SD rats were fad with high-fat diet for 4 weeks and then were injected STZ (30 mg· kg- 1 ) to induce the type 2 diabetic rats.Once the T2DM models were set successfully, rats were randomly divided into normal control group, diabetes model ( DM ) group, berberine ( 30 mg· kg - 1 ) group, GLPs of low ( GLPs-L), middle ( GLPs-M ) and high-dose (GLPs-H) group ( GLPs were orally given 200,400,800 mg · kg-1 ).After 12 weeks' treatment, the content of fasting blood glucose and AGEs in serum were detected.The expressions of AGEs and RAGE in aortas pectoralis were measured both by immunohistochemistric assays and westernblot analysis.Result: Compared with DM group, the content of blood glucose and AGEs in serum were significantly decreased in GLPs-H group and GLPs-M group (P <0.01 ).Compared with DM group, the expressions of AGEs and RAGE in aorta pectoralis were decreased in other groups, especially in GLPs-H group(P <0.01 ).Conclusion: GLPs could low blood glucose and protect aortas effectively.The mechanisms may be involved in down-regulation the expressions of AGEs and RAGE in aortal tissue.%目的:研究灵芝多糖对2型糖尿病大鼠胸主动脉糖基化终末产物及其受体的影响,探讨灵芝多糖对糖尿病大鼠主动脉的保护机制.方法:SD大鼠经4周高脂饮食后腹腔注射链脲佐菌素(STL)30mg·㎏-1建立2型糖尿病(T2DM)模型.大鼠随机分为对照组、模型组、小檗碱阳性对照组、灵芝多糖低、中、高剂量组(200,400,800mg·㎏-1).给药治疗12周后,测定大鼠空腹血糖、血清中糖基化终末产物(AGES)含量,免疫组化法和蛋白印迹法测定胸主动脉AGES,RAGE蛋白的表达情况.结果:灵芝多糖高、中剂量组与模型组

  13. AGEs对SH-SY5Y细胞增殖、凋亡以及阿尔茨海默病相关mRNA的影响%Effect of advanced glycation end products on proliferation and apoptosis of SH-SY5Y cells and mRNA expression of AD related proteins

    Institute of Scientific and Technical Information of China (English)

    黎雪松; 朱元昌; 倪膺佳; 刘冠杰; 韦建鸽; 钟鸣; 刘誉

    2011-01-01

    目的 研究晚期糖基化终产物(AGEs)对人神经母细胞瘤SH-SY5Y细胞株增殖、凋亡以及AD相关mRNA的影响。 方法 利用小牛血清白蛋白(BSA)和葡萄糖体外制备BSA-AGEs;将SH-SY5Y细胞与不同浓度BSA-AGEs保温后,MTT法测定SH-SY5Y细胞的增殖率,流式细胞仪测定细胞凋亡和细胞周期的变化,RT-PCR检测细胞中AD相关mRNA的表达水平。 结果 BSA-AGEs对SH-SY5Y细胞增殖有明显抑制作用,明显促进神经元的凋亡,细胞周期被阻滞于G1/G0期,呈药物浓度依赖性。RT-PCR结果表明,经过BSA-AGEs刺激后,IL-6、高迁移率族蛋白B1(HMGB1)、淀粉先质蛋白(APLP1) mRNA表达水平均明显升高。 结论 BSA-AGEs能有效抑制SH-SY5Y细胞的增殖,促进炎症细胞因子产生,诱导细胞凋亡,提示AGEs在AD的发生与发展过程中具有促进作用。%Objective To study the effect of advanced glycation end products (AGEs) on the proliferation, cell cycle and apoptosis of SH-SY5Y cells, and the mRNA expression of AD related protiens. Methods Bovine serum albumin-AGEs (BSA-AGEs) were prepared by incubation of BSA with glucose in vitro. SH-SY5Y cells were incubated with different concentrations of BSA-AGEs. Cell proliferation was measured by MTT assay; cell cycle and apoptosis were determined by flow cytometry; mRNA levels of APLP1, IL-6 and HMGB-1 were determined by RT-PCR. Results After incubation with BSA-AGEs for 48 h, SH-SYSY cell proliferation was significantly inhibited and cell apoptosis was induced; the cells were found to be arrested at G1/G0; these effects were dose-dependent. RT-PCR results showed that mRNA levels of IL-6, APLP1 and HMGB-1 were significantly up-regulated. Conclusion BSA-AGEs inhibit the cell proliferation and induce the apoptosis of SH-SY5Y cells, and stimulate the expression of some pro-inflammatory cytokines, suggesting a possible important role of AGEs in pathogenesis and development of AD.

  14. 子痫前期患者胎盘组织中晚期糖基化终产物受体和P-选择素的表达%Expression of receptor of advanced glycation end products and P-selectin in placenta of preeclampsia patients

    Institute of Scientific and Technical Information of China (English)

    杨玲竹; 李亚敏

    2011-01-01

    Aim :To explore the role of receptor of advanced glycation end products (RAGE) and P-selectin in the development of preeclampsia (PE). Methods:SP method and RT-PCR analysis were used to detect the expression of RAGE and P-selectin protein and mRNA in placenta tissue from 40 cases of PE (20 cases of mild PE, 20 cases of severe PE) and 30 cases of normal term pregnant. Results: All groups showed RAGE and P-selectin positive pigmentation in the placenta.RAGE protein was mainly expressed in trophoblast cells, but there was a small amount in the vascular endothelial cells.P-selectin was mainly expressed in syncytiotrophoblast cells, vascular endothelial cells,and interstitial cells. There were significant differences among three groups on the expression of RAGE and P-selectin protein( F = 250.152 and 274. 044,P <0. 001 ) and mRNA( F =624. 550 and 708. 351 ,P <0. 001 ). Expression of RAGE and P-selectin mRNA was significantly higher in placenta tissue of PE group compared with that of control group ( P < 0.05 ), the levels of severe PE group were higher than those of mild PE group ( P < 0.05) , and there was a positive correlation between them of protein and mRNA expression ( r =0. 814 and 0. 796 ,P <0. 001 ). Conclusion:The high levels of RAGE and P-selectin in placenta tiusse in PE may be associated with the occurrence and development of PE, and both of them have synergies in the development of PE.%目的:探讨晚期糖基化终产物受体(RAGE)和P-选择素(P-selectin)在子痫前期(PE)发生发展中的作用.方法:采用免疫组织化学SP法和RT-PCR法检测30例正常孕妇(对照组)和40例PE患者(轻度20例、重度20例)胎盘组织中RAGE和P-selectin蛋白及mRNA的表达情况.结果:对照组与PE组胎盘组织内均有RAGE和P-selectin阳性表达,RAGE主要表达于滋养细胞.血管内皮细胞巾也有少量表达;P-seleetin主要表达于合体滋养细胞、血管内皮细胞及间质细胞.3组RAGE和P-seleetin蛋白(F=250.152

  15. 皮肤组织晚期糖基化终产物对高血压患者血管弹性功能影响的研究%Effect of advanced glycation end products in skin tissue on vascular elasticity in hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    喜杨; 孙宁玲; 姜娟; 杨文; 陈源源; 王鸿懿

    2013-01-01

    Objective To study the correlation between advanced glycation end (AGE) products and vascular elasticity in skin tissue of hypertensive patients. Methods One hundred and fifty-seven hypertensive patients were divided into hypertension group(n = 62),hypertension-)-diabetes melli tus(DM) group(n = 42) and hypertension+ DM+ coronary heart disease(CHD) group(n=53). Thirty-two persons who underwent health check served as a control group. AGE products in their skin tissue were detected with an invasive detector from DiagnOptics Company of Netherlands and expressed as auto-fluorescence (AF) spectrum value. Their carotid-femoral pulse wave velocity (cf-PWV) was measured with an artery elasticity analyzer from Complior Company of France. Re sults The AF spectrum value was significantly higher in hypertension group, hypertension+DM group and hypertension + DM+ CHD group than in control group(F<0. 01). The cf-PWV was significantly higher in hypertension group than in hypertension+DM+CHD group[(9. 27 ± 2. 13) m/s vs (11. 59 ± 3. 36)m/s,P<0. 01]. The AF positively correlated with the cf-PWV(r=0. 329, P = 0. 000) (indicating that the AF spectrum value is an important factor for hypertension. Conclu sion The AGE products in skin tissue of hypertensive patients play an important role in assess ment of vascular risks.%目的 探讨高血压患者皮肤组织晚期糖基化终产物(AGE)的变化特点及与血管弹性功能异常的相关性.方法 选择高血压患者157例,依据合并疾病分为高血压组62例,高血压合并糖尿病组(合并1组)42例,高血压合并糖尿病及冠心病组(合并2组)53例,同期选择健康体检者32例作为对照组.采用荷兰DiagnOptics公司AGE无创测量装置测定皮肤组织AGE水平,用皮肤自体荧光光谱(AF)值表示;采用法国Complior公司动脉弹性测定仪测定颈-股脉搏波传导速度(cf PWV).结果 与对照组比较,高血压组、合并1组和合并2组的皮肤AF明显升

  16. AGEs对兔软骨细胞TNF-α和MMP-13表达的影响及其机制研究%The effects of advanced glycation end products on expression of tumor necrosis factor-αand matrix metalloproteinase-13 in rabbit chondrocytes and its mechanism

    Institute of Scientific and Technical Information of China (English)

    陈铖; 马翅; 张莹; 肖钧; 蔡巍; 谭海涛

    2013-01-01

    目的:探讨晚期糖基化终末产物(AGEs)对兔软骨细胞肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶-13(MMP-13)的影响及可能机制。方法:不同浓度的AGEs与兔软骨细胞共孵育48h后采用RT-PCR方法检测TNF-α和MMP-13的mRNA表达量,试剂盒方法检测过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)水平,荧光探针法检测细胞内活性氧(ROS)水平。AGEs与兔软骨细胞共孵育的同时,分别加入AGEs受体的抗体(Anti-RAGE)及核因子-κB(NF-κB)的特异性阻断剂PDTC处理,同法检测TNF-α和MMP-13的mRNA表达量。结果:与AGEs共孵育48h后兔软骨细胞TNF-α及MMP-13表达明显增多,CAT、SOD活性降低,MDA、ROS含量增多,均呈浓度依赖性;分别加入Anti-RAGE 及PDTC 处理后软骨细胞TNF-α及MMP-13表达明显低于AGEs单独处理组(P0.05)。结论:AGEs能诱导软骨细胞TNF-α和MMP-13表达增多,其机制与激活RAGE,诱导ROS生成增多,激活NF-κB信号通路有关。%Objective To detect the effects of advanced glycation end products (AGEs) on expression of tu-mor necrosis factor-α(TNF-α) and matrix metalloproteinase-13(MMP-13) in rabbit chondrocytes and its mecha-nism. Methods The chondrocytes were incubated with different concentrations of AGEs for 48h, the expression of TNF-αand MMP-13 mRNA were detected by reverse transcription polymerase chain reaction(RT-PCR),the lev-el of catalase (CAT), Malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were detected by kits, and the level of ROS is measured by the method of Fluorescent probe. The effect of anti-RAGE(Receptor for AGEs) and PDTC(the inhibitor of NF-KB) on the expression of TNF-αand MMP-13 induced by AGEs were also measured by RT-PCR. Results After chondrocytes were incubated with AGEs, dose-dependly increased the ex-pression of TNF-αand MMP-13 (P0.05). Conclusion AGEs can induce the TNF-αand MMP-13 expression. It's mechanism may

  17. Advanced Glycation End Products Effect on the Proliferation of Human Periodontal Ligament Stem Cells and Its Effect on HSG and Cyclin D1 Expression%糖基化终末产物对人牙周膜干细胞增殖及相关基因HSG、cyclinD1表达的影响

    Institute of Scientific and Technical Information of China (English)

    陶庭亮; 邓超; 柳海; 周嵩琳; 徐清; 王云

    2015-01-01

    Objective:To investigate the effect of advanced glycation end products (AGEs) on the proliferation of human periodontal ligament stem cells (HPDLSCs).Methods:HPDLSCs were isolated by limited dilution of culture cells for single cell clone.The osteogenic differentiation capacity of HPDLSCs was evaluated by Alizarin red staining.The adipogenic differentiation capacity of HPDLSCs was evaluated by oil red staining.HPDLSCs were induced with different concentrations of AGEs,The proliferation of HPDLSCs was assayed by MTT,Real time quantitative reverse transcription polymerase chain reaction (real time PCR) was performed to detect the differences of gene expression between the control group and experimental group.Results:After 21 days induction,Alizarin red staining showed mineralization nodules were formed,oil red staining showed lipid droplets were formed.Different concentrations of AGEs had different effects on the PDLSCs proliferative capacity.High concentrations (100mg/L,200mg/L) significantly inhibited the proliferation of PDLSCs.Low concentration (1mg/L,10mg/L) had little effect on the proliferative capacity of PDLSCs.After 3 days,the expressions of cell cycle gene (cyclinD1) in the experimental group were lower than those in the control group,the expressions of HSG in the experimental group were higher than those in the control group (P<0.05).Conclusion:High concentrations of AGEs reduced the proliferation capacity of HPDLSCs,and changed the expressions of HSG and cyclinD1 mRNA levels.%目的:探讨糖基化终末产物(AGEs)对人牙周膜干细胞(HPDLSC)增殖能力以及增殖相关基因HSG、cyclinD1的影响.方法:体外组织块法和有限稀释法克隆化培养牙周膜干细胞;成骨、成脂诱导牙周膜细胞,对其进行干细胞鉴定;将培养出的牙周膜干细胞与不同浓度的AGEs共培养,MTT检测不同浓度下牙周膜干细胞增殖的改变;实时定量聚合酶链反应(real time PCR)检测AGEs刺激后HSG、cyclin D1表达

  18. [The role of nonenzymatic glycation and glyco-oxidation in the development of diabetic vascular complications].

    Science.gov (United States)

    Jakus, V

    2003-05-01

    Hyperglycaemia is considered to be the key causal factor in the development of diabetic complications. Poor glycemic control a significant changes of erythrocyte membrane fluidity, erythrocyte deformability and antioxidant status. Nonenzymatic glycation and glycoxidation with cascade of free radical reactions, oxidative and carbonyl stress may play an important role in the development diabetic micro- and macrovascular complications. The serum levels of specific and nonspecific advanced glycation end products (s-AGEs) have been found elevated in type 1 and type 2 diabetic patients. Levels of s-AGEs. may serve as useful biochemical marker for monitoring progression of diabetic complications and pathological processes. Accumulation of AGEs on tissue proteins increases with pathogenesis of diabetic complications and atherosclerosis. AGEs are believed to induce cellular oxidative stress through the interaction with specific cellular receptors. Carbonyl stress-induced tissue damage is caused by AGE precursors formed by hyperglycaemia, hyperlipidemia, nonenzymatic glycation, peroxidation of lipids and metabolis processes. The toxic effects of AGE precursors can not be directly antagonized by antioxidants. Only a small number of biological carbonyl scavengers like glutathione have been identified to date. For therapeutic intervention, nucleophilic compounds as aminoguanidine, pyridoxamine, OPB-9195, 2,3-diaminophenazone, carnosine and tenilsetam give promising results. These potential therapeutics have been proposed to trap AGE precursors. Studies in vitro showed that these AGE inhibitors have also the antioxidant and chelating activity. Angiotensin converting enzyme (ACE) and angiotensin II receptor antagonists also significantly attenuate AGE production. These drugs do not trap AGE precursors, but impact on the production of AGE precursors by chelating transition metals and inhibiting various oxidative steps in the process of glycoxidation, including the formation of

  19. Effect of caspase-dependent pathway on apoptosis of human gingival fibroblasts induced by advanced glycation end products%凋亡蛋白酶依赖性凋亡途径在晚期糖基化终产物诱导人牙龈成纤维细胞凋亡中的作用

    Institute of Scientific and Technical Information of China (English)

    刘开蕾; 俞少杰; 付云

    2011-01-01

    Objective To investigate the effect of synthesized advanced glycation end products (AGE) on apoptosis of human gingival fibroblasts(HGF) and the possible role of caspase-dependent pathway in the process of AGE-induced apoptosis.Methods HGF were incubated with AGE-human serum albumin (AGE-HSA).The activity of caspase-8,caspase-9 and caspase-3 were detected by microplate reader after 12 and 24 hours.HGF were incubated with caspase inhibitors for 1 hour,and then incubated with AGE-HSA for 24 hours,HGF was first stained by Hoechst33258 and observed under inverted microscope,and then double stained by annexin V and propidine iodide(PI) and observed by flow cytometry(FCM).The activity of caspase-3 was determined by caspase-3 assay kit and observed by microplate reader.Results Caspases activity of caspase-8,-9,-3 was 0.1097 ±0.0051,0.0965 ±0.0051 and 0.1280 ±0.0103 after 12 h of incubation with AGE-HSA and HGF,respectively,and 0.1558 ±0.0053,0.1308 ±0.0035 and 0.1954 ±0.0051 after 24 h of incubation with AGE-HSA and HGF,respectively ( P <0.05).Positive cells number was 247.7 ±32.4,200.1 ± 14.6,154.1 ± 14.4 and 131.3 ± 14.6 in caspase inhibitor groups by Hoechst33258 staining,respectively.Apoptotic rate was ( 25.57 ± 2.20 ) %,( 38.87 ± 3.31 ) %,( 17.17 ± 2.24 ) % and ( 14.73 ±2.48)% in caspase inhibitor groups by annexin V-PI staining,respectively.The difference between different groups was significant (P < 0.05 ).Caspase-3 activity was reduced to 0.1274 ± 0.0076,0.1465 ± 0.0062,0.1044 ±0.0051 in caspase inhibitor groups,respectively.The difference between different groups was significant(P < 0.05 ).Conclusions Apoptosis of HGF induced by AGE-HISA may be mainly through activation of caspase-dependant pathway in which cytoplasmic pathway may play a predominant role.%目的 观察晚期糖基化终产物(advanced glycation end products,AGE)对人牙龈成纤维细胞(human gingival fibroblasts,HGF)凋亡的诱导作用,同时

  20. Human Achilles tendon glycation and function in diabetes

    DEFF Research Database (Denmark)

    Couppé, Christian; Svensson, Rene Brüggebusch; Madsen, Mads Kongsgaard;

    2016-01-01

    Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between...... tissue cross-linking were greater in diabetic patients compared to controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g skin and joint capsule) may influence on foot gait. The difference in foot pressure distribution may contribute to the development...... of foot ulcers in diabetic patients....

  1. Glycation Reactivity of a Quorum-Sensing Signaling Molecule.

    Science.gov (United States)

    Tsuchikama, Kyoji; Gooyit, Major; Harris, Tyler L; Zhu, Jie; Globisch, Daniel; Kaufmann, Gunnar F; Janda, Kim D

    2016-03-14

    Reported herein is that (4S)-4,5-dihydroxy-2,3-pentanedione (DPD) can undergo a previously undocumented non-enzymatic glycation reaction. Incubation of DPD with viral DNA or the antibiotic gramicidin S resulted in significant biochemical alterations. A protein-labeling method was consequently developed that facilitated the identification of unrecognized glycation targets of DPD in a prokaryotic system. These results open new avenues toward tracking and understanding the fate and function of the elusive quorum-sensing signaling molecule. PMID:26890076

  2. Germanium recovery from gasification fly ash: evaluation of end-products obtained by precipitation methods.

    Science.gov (United States)

    Arroyo, Fátima; Font, Oriol; Fernández-Pereira, Constantino; Querol, Xavier; Juan, Roberto; Ruiz, Carmen; Coca, Pilar

    2009-08-15

    In this study the purity of the germanium end-products obtained by two different precipitation methods carried out on germanium-bearing solutions was evaluated as a last step of a hydrometallurgy process for the recovery of this valuable element from the Puertollano Integrated Gasification Combined Cycle (IGCC) fly ash. Since H(2)S is produced as a by-product in the gas cleaning system of the Puertollano IGCC plant, precipitation of germanium as GeS(2) was tested by sulfiding the Ge-bearing solutions. The technological and hazardous issues that surround H(2)S handling conducted to investigate a novel precipitation procedure: precipitation as an organic complex by adding 1,2-dihydroxy benzene pyrocatechol (CAT) and cetyltrimethylammonium bromide (CTAB) to the Ge-bearing solutions. Relatively high purity Ge end-products (90 and 93% hexagonal-GeO(2) purity, respectively) were obtained by precipitating Ge from enriched solutions, as GeS(2) sulfiding the solutions with H(2)S, or as organic complex with CAT/CTAB mixtures and subsequent roasting of the precipitates. Both methods showed high efficiency (>99%) to precipitate selectively Ge using a single precipitation stage from germanium-bearing solutions.

  3. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

    Science.gov (United States)

    Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P; Sze, Siu Kwan

    2016-05-18

    Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.

  4. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

    Science.gov (United States)

    Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P; Sze, Siu Kwan

    2016-01-01

    Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases. PMID:27189269

  5. Structural alterations of human serum albumin caused by glycative and oxidative stressors revealed by circular dichroism analysis.

    Science.gov (United States)

    Monacelli, Fiammetta; Storace, Daniela; D'Arrigo, Cristina; Sanguineti, Roberta; Borghi, Roberta; Pacini, Davide; Furfaro, Anna L; Pronzato, Maria A; Odetti, Patrizio; Traverso, Nicola

    2013-01-01

    The aim of this work was to evaluate the ability of oxidative and glycative stressors to modify properties of human serum albumin (HSA) by analyzing markers of glycation (pentosidine) and oxidation (advanced oxidative protein products (AOPPs)) and assessing fluorescence and circular dichroism. HSA was incubated for up to 21 days with ribose, ascorbic acid (AA) and diethylenetriamine pentacetate (DTPA) in various combinations in order to evaluate influences of these substances on the structure of HSA. Ribose was included as a strong glycative molecule, AA as a modulator of oxidative stress, and DTPA as an inhibitor of metal-catalyzed oxidation. Ribose induced a significant increase in pentosidine levels. AA and DTPA prevented the accumulation of pentosidine, especially at later time points. Ribose induced a mild increase in AOPP formation, while AA was a strong inducer of AOPP formation. Ribose, in combination with AA, further increased the formation of AOPP. DTPA prevented the AA-induced generation of AOPP. Ribose was also a potent inducer of fluorescence at 335nm ex/385nm em, which is typical of pentosidine. AA and DTPA prevented this fluorescence. Circular dichroism showed complex results, in which AA and DTPA were strong modifiers of the percentages of the alpha-helical structure of HSA, while ribose affected the structure of HSA only at later time points.

  6. A study on human serum albumin influence on glycation of fibrinogen

    International Nuclear Information System (INIS)

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [13C6] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein

  7. A study on human serum albumin influence on glycation of fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr, E-mail: Piotr.stefanowicz@chem.uni.wroc.pl

    2013-09-13

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

  8. Kinetic evaluation of the inhibition of protein glycation during heating.

    Science.gov (United States)

    Akıllıoğlu, H Gül; Gökmen, Vural

    2016-04-01

    This study aimed to investigate the kinetics of early stage of the Maillard reaction by a reversible bimolecular reaction mechanism and also to evaluate the compatibility of enzyme inhibition kinetics for calculating the inhibitory activity of protein anti-glycation agents. Model systems composed of ovalbumin, glucose, and anti-glycation agents (tannic acid or calcium ion) at different molar ratios were heated at 90 °C for different times in dry state or in solution. Heated samples were analysed for furosine, acid derivative of N-ε-fructoselysine (FL), to monitor the progression of the early glycation stage. Compared to a control, presence of calcium ions and tannic acid decreased FL formation significantly (p<0.05) during heating in dry state. Evaluation of the kinetic data revealed that calcium inhibited glycation of ovalbumin by a mixed non-competitive mechanism in both dry and in solution conditions; while the mode of inhibition by tannic acid was found to be purely non-competitive in the dry state. PMID:26593596

  9. Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

    DEFF Research Database (Denmark)

    Di Angelantonio, Emanuele; Gao, Pei; Khan, Hassan;

    2014-01-01

    IMPORTANCE: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE: To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of c...

  10. Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

    NARCIS (Netherlands)

    Di Angelantonio, Emanuele; Gao, Pei; Khan, Hassan; Butterworth, Adam S.; Wormser, David; Kaptoge, Stephen; Seshasai, Sreenivasa Rao Kondapally; Thompson, Alex; Sarwar, Nadeem; Willeit, Peter; Ridker, Paul M.; Barr, Elizabeth L. M.; Khaw, Kay-Tee; Psaty, Bruce M.; Brenner, Hermann; Balkau, Beverley; Dekker, Jacqueline M.; Lawlor, Debbie A.; Daimon, Makoto; Willeit, Johann; Njolstad, Inger; Nissinen, Aulikki; Brunner, Eric J.; Kuller, Lewis H.; Price, Jackie F.; Sundstrom, Johan; Knuiman, Matthew W.; Feskens, Edith J. M.; Verschuren, W. M. M.; Wald, Nicholas; Bakker, Stephan J. L.; Whincup, Peter H.; Ford, Ian; Goldbourt, Uri; Gomez-de-la-Camara, Agustin; Gallacher, John; Simons, Leon A.; Rosengren, Annika; Sutherland, Susan E.; Bjorkelund, Cecilia; Blazer, Dan G.; Wassertheil-Smoller, Sylvia; Onat, Altan; Ibanez, Alejandro Marin; Casiglia, Edoardo; Jukema, J. Wouter; Simpson, Lara M.; Giampaoli, Simona; Nordestgaard, Borge G.; Selmer, Randi; Wennberg, Patrik; Kauhanen, Jussi; Salonen, Jukka T.; Dankner, Rachel; Barrett-Connor, Elizabeth; Kavousi, Maryam; Gudnason, Vilmundur; Evans, Denis; Wallace, Robert B.; Cushman, Mary; D'Agostino, Ralph B.; Umans, Jason G.; Kiyohara, Yutaka; Nakagawa, Hidaeki; Sato, Shinichi; Gillum, Richard F.; Folsom, Aaron R.; van der Schouw, Yvonne T.; Moons, Karel G.; Griffin, Simon J.; Sattar, Naveed; Wareham, Nicholas J.; Selvin, Elizabeth; Thompson, Simon G.; Danesh, John

    2014-01-01

    IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA(1c)) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA(1c) values to conventional cardiovascular risk factors is associated with improvement in prediction of ca

  11. Monitoring the progress of non-enzymatic glycation in vitro

    International Nuclear Information System (INIS)

    The progress of in vitro non-enzymatic glycation of bovine serum albumin was followed by using 14C-glucose and a nitroblue tetrazolium assay, absorption and fluorescence spectroscopy, SDS gel electrophoresis and protease digestion. The number of adducts detectable using both 14C-tracers and a fructosamine assay remained low at physiological glucose concentrations, fewer than five adducts being detectable. When glucose concentrations > 1.0 M were used the number of adducts was found to greatly exceed the number of lysyl residues available in BSA, indicative of cross-linking between Maillard products. Incubation of BSA with glucose concentrations of up to 160 mM for one month produced no observable increase in molecular weight by SDS gel electrophoresis, showing that at physiological glucose concentrations, increases in molecular weight were minimal for short incubation periods. Increases in absorption were proportial to both the glucose concentration and the incubation time. Several absorption peaks, at 370, 488 and 554 nm, were consistent in appearance throughout the course of each incubation. Fluorescence spectroscopy of the modified proteins showed a disappearance of the fluorescence associated with peptide bonds and aromatic residues and the appearance of a broad peak at longer wavelengths due to the wide range of absorptive/fluorescent wavelengths of the developing Maillard products. Protease digestion gave similar patterns with non-glycated and glycated protein, suggesting that glycation did not block digestion sites, and that partial digestion did not cause significant further exposure of susceptible sites. Our results show that while glycation ultimately results in protein conformational changes and the formation of large molecular weight species, these occur at a relatively late stage in the maturation of protein Maillard products, after ≥ nine months of incubation with glucose concentration of ≥ 20 mM. Monitoring of AGE maturation in vitro is better

  12. Physicochemical Changes and Glycation Reaction in Intermediate-Moisture Protein-Sugar Foods with and without Addition of Resveratrol during Storage.

    Science.gov (United States)

    Sheng, Zhanwu; Gu, Mantun; Hao, Wangjun; Shen, Yixiao; Zhang, Weimin; Zheng, Lili; Ai, Binling; Zheng, Xiaoyan; Xu, Zhimin

    2016-06-22

    An intermediate-moisture food (IMF) model consisting of whey protein isolate and glucose and an IMF model fortified with resveratrol were used to study the effect of resveratrol on physicochemical changes and glycation of protein-sugar-rich foods during storage. The water activity (aw) of the storage was controlled at 0.75 or 0.56. The browning rate or hardness of fortified IMFs was significantly lower than that of IMFs after 45-day storage. The rate of Maillard reaction in the samples stored at aw 0.56 was higher than that of samples stored at aw 0.75. The fortified IMFs had lower levels of AGEs (advanced glycation end products), CML (N(ε)-(carboxymethyl)-l-lysine), and insoluble protein during storage. The inhibition capability of resveratrol against glycation was also confirmed by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), liquid chromatography mass spectrometry (LC-MS), and Fourier transform infrared spectroscopy (FTIR) analysis to monitor glycated proteins and protein aggregation in the samples. The results of this study suggested that resveratrol could be used as an inhibitor to reduce the formation of undesirable AGEs and other Maillard reaction products in foods during storage. PMID:27218138

  13. Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells.

    Science.gov (United States)

    Sun, Nan; Yang, Li; Li, Yingbin; Zhang, Hua; Chen, Hong; Liu, Duan; Li, Qingnan; Cai, Dehong

    2013-08-01

    Advanced oxidation protein products (AOPPs) as a novel marker of oxidative stress, are involved in a variety of diseases, including osteoporosis. Although a number of studies have shown the possible functions of AOPPs in biological processes, little is known about the role of AOPPs in the pathogenesis of osteoporosis. In this study, we aimed to investigate the effect of AOPPs on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (MSCs). MSCs, isolated from bone marrow, were cultured in the absence or presence of AOPPs (50, 100, 200 and 400 mg/ml). MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase (ALP) activity, the mRNA expression of ALP and collagen I and bone nodule formation were detected to assess osteogenic differentiation. Reactive oxygen species (ROS) generation was analyzed with the probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The expression of receptor of advanced glycation end-products (RAGE) at the mRNA and protein level was detected by real-time PCR and western blot analysis, respectively. Compared with the control group, AOPPs inhibited MSC proliferation in a dose- and time-dependent manner. Moreover, AOPPs induced a significant reduction in ALP activity, as well as a decrease in ALP and collagen I mRNA levels in the MSCs; bone nodule formation was also inhibited. Furthermore, AOPPs increased ROS generation in the MSCs, and upregulated the expression of RAGE at the mRNA and protein level. These results suggest that AOPPs inhibit the proliferation and osteogenic differentiation of MSCs, possibly through the AOPPs-RAGE-ROS pathway; this may be an important mechanism in the development of osteoporosis.

  14. Impact of interaction of advanced glycation end product and its receptor on podocytes apoptosis%晚期糖基化终末产物与其受体相互作用对足细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    于青; 袁伟杰; 刘智辉; 姚建

    2008-01-01

    目的 探讨可溶性与复合型晚期糖基化终末产物(AGE)与晚期糖基化终末产物受体(RAGE)的相互作用对足细胞凋亡的影响.方法 以可溶性(CML-BSA、AGE-BSA)和复合型(AGE修正胶原IV)AGE刺激小鼠足细胞,并用浓度分别为10、50、100 mg/L的AGE刺激细胞,应用TUNEL染色和荧光激活细胞分类(FACS)法来计数凋亡和坏死的足细胞.用RAGE iRNA转染足细胞后,以同样剂量的可溶性和复合犁AGE刺激足细胞,观察凋亡情况的改变.结果 可溶性和复合型AGE均町诱导小鼠足细胞凋亡,复合型AGE引起的足细胞凋亡是可溶性AGE的2~3倍(均P<0.01).AGE呈剂最依赖性引起足细胞凋亡.用RAGEiRNA转染足细胞,降低60%~70%RAGE基因活性后,可溶性AGE引起的凋亡率明显下降,复合型AGE诱导的凋亡有下降趋势,但不明显.只有在AGE 100 mg/L刺激后才发牛细胞坏死.结论 可溶性AGE主要通过与RAGE相互作用引起足细胞凋亡,复合型AGE部分通过与RAGE相互作用诱导足细胞凋亡.减少AGE生成和RAGE表达可能是预防肾脏病进展的重要途径.%Objective To study the effects of the interaction of advanced glycation end products (AGEs) and the receptor of AGEs (RAGE) on apoptosis of mice podocytes. Methods Podocytes were exposed to soluble AGEs such as bovine serum albumin (BSA), carboxymethyl-lysin (CML)-BSA, AGE-BSA and matrix-bound AGEs (AGE-modified collagen Ⅳ ), and to different concentrations of AGE, such as 10 mg/L, 50 mg/L, 100 mg/L. Apoptosis was assessed by TUNEL staining. Fluorescence-activated cell sorting (FACS) was used for the quantification of apoptotic andnecrotic podocytes after Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) labeling. Apoptosis was described as the ratio of apoptotic cells to the total number cells under the high-power field, siRNA was transfected into podocytes through combining Dharmacon on Targetplus SMART pool siRNA reagents and Amaxa RNAi

  15. Influence of Advanced Glycation End Products on the Function of Schwann Cells in Vitro and Related Mechanism%糖基化终产物对雪旺细胞体外功能的影响及其机制的研究

    Institute of Scientific and Technical Information of China (English)

    张媚; 张临洪

    2013-01-01

    advanced glycation end products ( AGEs ) on rat sciatic nerve - derived Schwann cells in vitro and investigate the change of inflammatory factors in order to provide a novel therapeutic target of peripheral neuropathy in diabetes patients.Methods Primary sciatic nerve - derived Schwann cells from 3 - day neonatal SD rats were obtained, purified and then identified by immunocytochemistry staining.The Schwann cells were divided into seven groups and were treated respectively with pure culture medium ( control group ), 20 μg/ml BSA, 20 μg/ml AGEs, 50 μg/ml BSA, 50 μg/ml AGEs, 100 μg/ml BSA and 100 μg/ml AGEs respectively.Then the proliferation, migration, apoptosis and Caspase -3 mRNA of treated cells were detected.After that, the Schwann cells were divided into four groups and then were treated with pure culture medium ( control group ), 50 μg/ml BSA, 50 μg/ml AGEs and 50 μg/ml AGEs + 10 μg/ml anti - receptor of AGEs ( RAGE ) antibody respectively.The activity of NF - ΚB and the level of tumor necrosis factor α ( TNF -α) and interleukin 6 ( IL - 6 ) were measured.Results ( 1 ) Compared with the control group, there were no statistically significant difference on every detective parameter ( proliferation, migration, apoptosis and Caspase - 3 mRNA ) in BSA groups ( P > 0.05 ) .The cell proliferation, migration in AGEs groups became significantly weaker than those in BSA groups and control group ( P 0.05 ).Conclusion AGEs can inhibit the proliferation capacity of Schwann cells and accelerate the apoptosis in vitro, probably through promoting the production of inflammatory factors which are harmful to cells.

  16. 可溶性晚期糖基化终末产物受体在急性呼吸窘迫综合征患者诊断及预后评估中的应用价值%Application Value of Soluble Receptor of Advanced Glycation End products in the Diagnostic and prognostic Assessment of patients With Acute Respiratory Distress Syndrome

    Institute of Scientific and Technical Information of China (English)

    胡占升

    2014-01-01

    目的:探讨可溶性晚期糖基化终末产物受体(sRAGE)在急性呼吸窘迫综合征(ARDS)患者诊断及预后预测中的价值。方法选取2012年3月-2013年3月入住辽宁医学院附属第一医院重症监护病房的 ARDS 患者60例为 ARDS 组,根据氧合指数(PaO2/ FiO2)将 ARDS 组分为轻度 ARDS 组(23例)、中度 ARDS 组(23例)及重度ARDS 组(14例),根据预后分为死亡组(18例)及存活组(42例);另选择同时期入住重症监护病房的非 ARDS 患者60例为非 ARDS 组。采用酶联免疫吸附试验(ELISA)法检测患者血浆 sRAGE 水平,记录患者PaO2/ FiO2。结果ARDS 组较非 ARDS 组患者 sRAGE 水平升高,PaO2/ FiO2降低,差异有统计学意义(P é0.05)。不同严重程度 ARDS 组患者 sRAGE 水平及PaO2/ FiO2比较,差异均有统计学意义(P é0.05);其中中度 ARDS 组、重度 ARDS 组较轻度 ARDS组,重度 ARDS 组较中度 ARDS 组患者 sRAGE 水平升高,PaO2/ FiO2降低,差异有统计学意义(P é0.05)。死亡组较存活组 ARDS 患者 sRAGE 水平升高,PaO2/ FiO2降低,差异有统计学意义( P é0.05)。直线相关性分析显示,ARDS组患者 sRAGE 水平与PaO2/ FiO2呈负相关(r =-0.949,P =0.0002)。结论 sRAGE 在 ARDS 患者预后预测方面存在价值,可作为评价 ARDS 预后的一个生化标记物;在诊断方面可能存在一定价值,有待于进一步研究验证。%Objective To discuss the application value about soluble receptor for advanced glycation end products (sRAGE)in the diagnostic and prognostic assessment of patients with acute respiratory distress syndrome(ARDS)in the inten-sive care unit(ICU). Methods 60 ARDS patients admitted to the First Affiliated Hospital of Liaoning Medical University from March 2012 to March 2013 were selected. The patients were divided into mild group(23 cases),moderate group(23 cases)and severe group(14 cases)based on o

  17. 妊娠期糖尿病母鼠血清晚期糖基化终产物与子鼠心脏发育异常的关系%Relationship between the advanced glycation end products in gestational diabetes mellitus rats and its newborns heart development

    Institute of Scientific and Technical Information of China (English)

    柳国胜; 吴瑕; 刘海英; 赵立华; 康举龄; 李小毛; 肖作源

    2009-01-01

    目的 探讨妊娠期糖尿病(GDM)母鼠血清晚期糖基化终产物(AGE)在GDM致胎儿心脏发育异常中的作用.方法 54只SD孕鼠随机分为GDM组(30只)和对照组(24只).GDM组孕鼠给予2%链脲霉素40 mg/kg,对照组注射等量柠檬酸缓冲液.孕鼠于孕13、16、19 d随机剖宫取胎,观察胚胎心脏异常情况,检测母鼠血清AGE水平、免疫组化法检测AGE受体(RAGE)在子鼠心脏组织的表达情况.结果 GDM组各时间点子鼠心脏发育异常比例较对照组高(P<0.01).GDM组孕鼠用药3 d后血糖水平明显高于对照组(P<0.01),尿糖均阳性.GDM组AGE水平在孕13、16和19 d时[(5.72±0.68)AU/mg、(7.31±0.29)AU/mg和(7.77±0.39)AU/mg]较对照组[(4.45±0.27)AU/mg、(4.71±0.35)AU/mg和(4.37±0.44)AU/mg]显著升高(t=6.142、16.295和9.399,P均<0.01);孕鼠AGE水平与孕鼠血糖(r=0.717,P=0.000)及子鼠心脏畸形数(r=0.994,P=0.000)呈正相关.子鼠心脏RAGE表达与心脏畸形数呈正相关(r=0.638,P=0.004).结论 孕鼠血清AGE升高可能是胚胎心脏发育异常的重要因素.%Objective To explore the effect of advanced glycation end product(AGE) in serum of maternal rats with gestational diabetes mellitus (GDM) on the heart development of their offsprings. Methods Fifty-four SD rats were randomly assigned into control group (n= 24) and GDM group (n=30) which were established by administration of streptozotocin intra-abdominally. On the gestational age of 13, 16, 19 days, all rats underwent hysterectomy to obtain the fetal heart tissues. Serum level of AGE and blood glucose level of maternal rats were tested. The expression of receptor AGE (RAGE) in fetal cardiac tissue were detected by immunohistoehemistry. Results The incidence of fetal heart defect in GDM group was significantly higher than the control group at each time point (P<0.01). Rats in GDM group had higher blood glucose level at each time point (P<0.01). The AGE levels of GDM group on gestational age of 13, 16 and 19 day

  18. Relationship between GDM maternal advanced glycation end products level and fetal birth defects and it's clinical significance%GDM孕妇血清晚期糖基化终产物水平与其胎儿出生缺陷的关系及临床意义

    Institute of Scientific and Technical Information of China (English)

    汤栩文; 林斯; 谢晓斌

    2012-01-01

    目的:检测妊娠期糖尿病(GDM)孕妇血清及脐血血清中晚期糖基化终产物(AGE)的水平,并观察胎盘组织中AGE受体(RAGE)的表达,探讨AGE与胎儿出生缺陷的关系及其在产前筛查中的临床意义.方法:选择经产前筛查诊断为胎儿畸形或胎死宫内的GDM孕妇作为病例组(42例),随机选择GDM无胎儿异常孕妇作为GDM组(30例),无妊娠合并症的健康孕妇作为健康对照组(30例).采用酶联免疫法检测孕妇血清及脐血血清AGE水平;采用免疫组化方法检测胎盘组织中RAGE蛋白的表达.结果:病例组、GDM组、健康对照组脐血血清AGE水平分别为(223.9±54.6),(160.7±37.2),(108.3+15.8) μg/L,三组差异显著(P<0.05);病例组、GDM组、健康对照组孕妇血清AGE水平分别为(169.1±14.3),(105.4±17.2),(80.6±11.4) μg/L,三组亦有显著差异(P<0.05);病例组孕妇血清与脐血血清中AGE水平呈正相关(r=0.863,P<0.01);病例组、GDM组及健康对照组胎盘组织中RAGE的阳性表达率分别为87.5%、53.1%、29.6%,三组差异显著(P<0.05).结论:GDM孕妇高AGE血症是导致出生缺陷的危险因素,孕妇血清AGE水平可作为GDM出生缺陷的产前筛查指标.%Objective:To detect serum advanced glycation end products(AGE) level in gestation diabetic mother( GDM) gestational period and fetal cord blood, and observe the RAGE protein expression in placenta. To explore the clinical significance of relationship be-tween fetal birth defects and AGE levels in prenatal screening. Methods: Gestational diabetes pregnant woman confirmed fetalmalformation or fetal death by prenatal diagnosis were enrolled as the study group, total of 42 cases; Randomly selected the GDM fetal normalities pregnant women,as the GDM group,30 cases;another 30 cases of the normal pregnant women wre select-ed randomly as healthy control group. Maternal peripheral blood and the specimens of fetal cord blood specimens were collected to detect AGE

  19. Relationship between Advanced Glycation End Products and Perinatal Outcome of Gestational Diabetes Patients%晚期糖基化终产物水平及其受体的表达与妊娠期糖尿病围生儿结局关系的研究

    Institute of Scientific and Technical Information of China (English)

    汤栩文; 林斯; 谢晓斌

    2012-01-01

    Objective:To explore the relationship between serum advanced glycation end products (AGEs) level in gestation diabetic(GDM) patients and their perinatal outcomes, and to observe the RAGE protein expression in placenta. Methods: Recruit 100 cases pregnant women diagnosed with GDM between 24-28 weeks gestational age as the observation group, and another 50 cases of normal pregnant women of corresponding age as the study control. The blood samples of GDM patients was extracted ,blood glucose, HbAic. AGE was determined. The placentas were cryopreservated immediately after delivery for the analysis of tissue expression of RAGE protein. And the maternal and infant clinical information were collected, The patients were also divided into normal perinatal group and abnormal perinatal group according to their perinatal outcomes. Results:①GDM groups had higher serum AGEs levels and fasting blood glucose compared to the control group (P0. 05), but the level of serum AGEs remained higher. ③Abnormal perinatal outcome in GDM had significantly higher maternal serum AGEs level than that in controls with normal perinatal outcome( P<0.05) . ④Logistic regression analysis showed that AGEs was a predictor of adverse perinatal outcome in GDM( OR =6.197,P< 0.001, 95% Cl: 2.514 ~ 15.453). ⑤The RAGE protein expression in the placenta was also higher in the abnormal perinatal group than that in normal perinatal group and control group. Conclusions: High serum AGEs is a negative factor for the GDM perinatal outcome, High levels of AGEs can be used as a abnormal perinatal outcome predictor in GDM patients.%目的:探讨妊娠期糖尿病(GDM)孕妇血清晚期糖基化终产物(AGEs)水平与围生儿结局间的关系,并观察晚期糖基化终产物受体(RAGE)蛋白在胎盘组织中的蛋白表达.方法:选择孕24~28周来我院产前检查被诊断患有GDM的孕妇100例为研究对象(GDM组),另选择同孕期、相应年龄的正常妊娠妇女50例作为正常对照组.

  20. Effects of gastrodine on expression of inflammatory cytokines in nerve microglia cell induced by advanced glycation end products%天麻素对终末糖基化产物诱导神经小胶质细胞炎症因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    张媛元; 毛瑞阳; 杜晓红; 刘毅

    2011-01-01

    Objective To investigate the effects of gastrodine (GAS) on the expression of IL-1β and IL-6 in nerve microglia BV-2 cell of mice induced by different concentrations of advanced glycation end products (AGEs) and GAS intervention.Methods The cultured BV-2 cells of mice were divided into AGEs group, GAS (12.5, 25, 50, and 100 mg/L) groups, which were cultured for 18 h to observe the changes of cell morphology.The levels of IL-1β and IL-6 in the cell culture supernate were determined by enzyme linked immunosorbent assay (ELISA) and the expressions of IL-lβ and mRNA were analysed by reverse transcriptase polymerase chain reaction (RT-PCR).Results Observed under an inverted microscope, microglia is mostly quiescent and less protruding in control group; Most cell processes were more and amoeba-like in AGEs group, which was most obviously at the concentration of 300 mg/L.Cell processes in GAS groups reduced less than those in AGEs groups, of which the least was in GAS group at concentration of 50 mg/L.Compared with the control group, the levels of IL-lβ and IL-6 in supernatants of cell culture in AGEs group and the expressions of IL-1β and IL-6 mRNA increased with significant difference (P<0.05).Compared with AGEs groups, the levels of IL-1β and IL-6 in supernatants of cell culture in AGEs group and the expressions of IL-1β and IL-6 mRNA obviously decreased, there were significant differences in AGE groups at the concentrations of 25, 50, and 100 mg/L (P<0.05), among which the decrease was most significant in the AGE group of 50 mg/L (P<0.01).Conclusion AGEs could induce that nerve microglia produce IL-1β and IL-6 and GAS could partly inhibit the induction of AGEs on microglia.%目的 观察终末糖基化产物(AGEs)对小鼠神经小胶质细胞BV-2炎症因子白细胞介素(IL-1β、IL-6)表达的影响及天麻素的干预效应.方法 将体外培养的小鼠小胶质细胞分成对照组、AGEs组、天麻素(12.5、25、50、100 mg/L)组,培养18 h,

  1. 银杏叶提取物、α-硫辛酸对糖尿病大鼠肾组织中糖基化终产物及其受体RAGE表达的影响%Extract of Ginkgo biloba and α-lipoic Acid Attenuate Advanced Glycation End Products Accumulation and RAGE Expression in Diabetic Nephropathy Rats

    Institute of Scientific and Technical Information of China (English)

    李雪竹; 严海东; 王俊; 江薇

    2011-01-01

    Objective To investigate the accumulation of advanced glycation end products (AGEs) and expression of receptor for AGEs (RAGE) in streptozocin (STZ)-induced diabetic nephropathy in rats, and the role of antioxidants on the AGEs-RAGE signaling.Methods Diabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg, and randomly divided into the DN group (n=12, treated with normal saline by intraperitoneal injection, once daily), the extract of Ginkgo biloba (EGb) group ( n =14, treated with EGb 300 mg/kg by oral administration, once every other day), and the α-lipoic add (ALA) group ( n =12, treated with ALA at the dose of 35 mg/kg by intraperitoneal injection, once every other day).Rats of the normal control group (n=10) were given vehicle dtrate buffer at the dose of 60 mg/kg.Rats were sacrificed at the 12th week and the 20th week of this study.The four groups were compared in terms of body weight, blood glucose, renal function, 24-h urine protein.Renal pathological changes were observed by PAS staining.Oxidative stress indices were detected using spectrophotometry.The concentrations of AGEs were measured using fluorospectrophotometry, and the expressions of RAGE were detected by Real-time PCR and Western blot.Results Compared with the normal control group, the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week.The pathological tissue staining showed dilated glomerular mesangium, proliferated glomerular matrix, vacuolar degeneration of the renal tubular epithelium.Malonaldehyde (MDA) levels and 8-hydroxide radical guanine deoxyriboside (8-OHdG) levels increased, and catalase (CAT) and reduced glutathione hormone (GSH) levels decreased.The AGEs contents in serum and renal tissue homogenate increased.The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week.The 24-h udne protein quantitation was reduced in the EGb group

  2. Value of serum advanced glycation end products-peptide in the screening of diabetes mellitus in a community-based population of high-risk diabetics%血清糖基化终产物-肽在社区糖尿病高危人群中的筛查价值

    Institute of Scientific and Technical Information of China (English)

    谢作玲; 张林; 王艳萍; 贺佳佳; 周祎; 雷程灏; 邱山虎; 孙子林

    2012-01-01

    Objective To explore the value of serum advanced glycation end products-peptide (AGE-P) in the screening of diabetes mellitus in a community-based population of high-risk diabetics.Methods A total number of 857 adult high-risk diabetics from a community-based population underwent 75 g oral glucose tolerance test (OGTF).Blood samples were drawn to measure the levels of fasting blood glucose (FBG),postprandial blood glucose (2 hPG) and glycosylated hemoglobin A1c (HbA1c).And blood samples were also collected to determine the serum level of AGE-P with the technique of flow injection analysis.Receiver operating characteristic (ROC) curve was plotted to assess the screening value of serum AGE-P in diabetes mellitus.Pearson correlation analysis was conducted to evaluate the association between serum AGE-P and FBG,2 hPG,HbA1c,body mass index (BMI),waist-to-hip ratio (WHR) and age.Results Among them,218 adults were diagnosed with diabetes based on the 2010 American Diabetes Association (ADA) criteria.According to the ROC curve,the optimal cut-point of serum AGE-P for diagnosing diabetes was 10.22 mg/L (a peak height of 25.39 mm) with sensitivity of 84.1%,specificity of 88.3% and positive predictive value of 71%.The area under curve (AUC) of serum AGE-P,FBG,2 hPG and HbA1c for diagnosing diabetes was 0.924,0.905,0.951 and 0.874 respectively.When comparing AUC between serum AGE-P and HbA1c,FBG and 2 hPG,statistical significance was only found in the comparisons between serum AGE-P and HbA1c (P < 0.025).Pearson correlation analysis showed that serum AGE-P was highly positively correlated with HbA1c,significantly positively correlated with FBG and 2 hPG and slightly positively correlated with WHR and age (all P < 0.05).But there was no correlation with BMI.Conclusions Serum AGE-P may be used for the screening of diabetes in the community-based population of high-risk diabetics.And it is even superior to HbA1c.%目的 探讨血清糖基化终产物-肽(AGE-P)在社

  3. Effect of advanced glycation end products on oxidative stress and apoptosis of SH-SY5Y cells%糖基化终末产物对SH-SY5Y细胞氧化应激及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    董传芳; 刘雪平; 王美霞; 徐松; 殷青青; 孙志坚; 游丽

    2012-01-01

    Objective To investigate the effect of advanced glycation end products (AGEs) on apoptosis of SH-SY5Y cells, and to further explore the relationship between AGEs and the mechanism of Alzheimer disease. Methods SH-SY5Y cells were treated with different concentrations of AGE-BSA for 48 h, or with AGE-BSA (200 μg/mL) for different times. Cell apoptosis was detected by flow cytometry (FCM) to determine the best concentration and time of AGE-BSA . SH-SY5Y cells were randomly divided into six groups; the normal control group, the BSA control group, the AGE-BSA group, the AGE-BSA + RAGE antibody group, the AGE-BSA + Alpha lipoic acid (ALA) group, and the AGE-BSA + diphenyleneiodonium (DPI) group. Cell apoptosis was detected by FCM and Hoechst staining, the level of ROS was evaluated by the 2', 7'-dichlorofluorescein diacetate (DCFH-DA) method, and expression of Caspase-12 was analyzed by Western blot. Results AGE-BSA induced SH-SY5Y cells apoptosis in a time-and concentration-dependent manner. After treatment with 200 μg/mL of AGE-BSA for 48 hours, apoptosis of SH-SY5Y cells was significantly increased to (16. 8 ± 1.27) % from (2.23 ± 0.08) % (P<0.05). Apoptosis-like cells could be found after Ho-echst staining of nuclei, the level of ROS and expression of Caspase-12 statistically increased compared with the normal group (P<0.05). Compared with the AGE-BSA group, apoptosis of cells, level of ROS and expression of Caspase-12 in the AGE-BSA + RAGE-Ab group, the AGE-BSA + ALA group and the AGE-BSA + DPI group were significantly decreased (P<0.05). Conclusion AGEs could induce the production of ROS and activation of Caspase-12, which may be involved in apoptosis of SH-SY5Y cells induced by AGEs. Blocking the combination of AGEs and its receptor (RAGE) or reducing production of ROS may protect against AGEs-induced SH-SY5Y apoptosis.%目的 研究糖基化终末产物( AGEs)对人神经母细胞瘤细胞(SH-SY5Y)凋亡的影响,探讨AGEs与阿尔茨海默病(AD

  4. Influence of glycated low density lipoprotein on the proliferation,expression of intercellular adhesion molecule-1,von Willebrand factor of human umbilical endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LU Jun; LIU Hui-ying; ZHANG Xiu-zhen; LEI Tao

    2009-01-01

    @@ Diabetes mellitus known as its macro-and microangiopathy has caused thousands of mortality per year.Recent researches showed that hyperglycemia,advanced glycation end products(AGEs)and some other factors acted on the process of atherogenesis.AGEs can combine with receptors of AGEs(RAGEs),which exist on the vascular endothelium,smooth muscle cells,macrophage,lymphocyte and so on.

  5. Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract.

    Science.gov (United States)

    Bahmani, Fereshteh; Bathaie, Seyedeh Zahra; Aldavood, Seyed Javid; Ghahghaei, Arezou

    2016-01-01

    The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of α-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited α-crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of α-crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on α-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract. PMID:26821002

  6. Glycation of bovine serum albumin by ascorbate in vitro: Possible contribution of the ascorbyl radical?

    Science.gov (United States)

    Sadowska-Bartosz, Izabela; Stefaniuk, Ireneusz; Galiniak, Sabina; Bartosz, Grzegorz

    2015-12-01

    Ascorbic acid (AA) has been reported to be both pro-and antiglycating agent. In vitro, mainly proglycating effects of AA have been observed. We studied the glycation of bovine serum albumin (BSA) induced by AA in vitro. BSA glycation was accompanied by oxidative modifications, in agreement with the idea of glycoxidation. Glycation was inhibited by antioxidants including polyphenols and accelerated by 2,​2'-​azobis-​2-​methyl-​propanimidamide and superoxide dismutase. Nitroxides, known to oxidize AA, did not inhibit BSA glycation. A good correlation was observed between the steady-state level of the ascorbyl radical in BSA samples incubated with AA and additives and the extent of glycation. On this basis we propose that ascorbyl radical, in addition to further products of AA oxidation, may initiate protein glycation. PMID:26202868

  7. Glycation of bovine serum albumin by ascorbate in vitro: Possible contribution of the ascorbyl radical?

    OpenAIRE

    Sadowska-Bartosz, Izabela; Stefaniuk, Ireneusz; Galiniak, Sabina; Bartosz, Grzegorz

    2015-01-01

    Ascorbic acid (AA) has been reported to be both pro-and antiglycating agent. In vitro, mainly proglycating effects of AA have been observed. We studied the glycation of bovine serum albumin (BSA) induced by AA in vitro. BSA glycation was accompanied by oxidative modifications, in agreement with the idea of glycoxidation. Glycation was inhibited by antioxidants including polyphenols and accelerated by 2,​2′-​azobis-​2-​methyl-​propanimidamide and superoxide dismutase. Nitroxides, known to oxid...

  8. Glycation of Liver Cystatin: Implication on its Structure and Function.

    Science.gov (United States)

    Mustafa, Mir Faisal; Bano, Bilqees

    2016-09-01

    The increased level of reducing sugars and their derivatives in a diabetic condition has been the main cause of protein related complications. The changes in native state of proteins upon glycation induce loss in the function and structure of proteins. This further leads to cell damage and accumulation of immune system inducing AGE formation. Here in the present study cystatin was purified from liver (BLC) through affinity chromatography and was incubated with glucose, fructose and ribose. Changes were observed in the intensity of Trp absorption at 280 nm as well as AGE's specific fluorescence at 435 nm upon excitation at 370 nm to monitor the formation of BLC-sugar adducts. Protein intrinsic fluorescence showed marked conformational changes when BLC was incubated with D-ribose, glucose and fructose. Glycation with D-ribose induces BLC to misfold rapidly into an intermediate state retaining a low percentage of α-helical content compared to fructose and glucose as revealed by far-UV CD data. Furthermore, a caseinolytic assay of papain in presence of glycated liver cystatin showed decreased activity in the protein induced by these reducing sugars. Ribose had more effect on the structure as well as the function of liver cystatin followed by fructose and least for glucose. Absorption spectroscopy shows change in BLC and formation of AGE's. These results shows that liver cystatin-cathepsin imbalance is compromised in diabetic state which may lead to improper balance of proteinases leading to cirrhosis or liver damage. PMID:27351669

  9. SERUM MAGNESIUM, LIPID PROFILE AND GLYCATED HAEMOGLOBIN IN DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Sunanda Vusikala

    2016-07-01

    Full Text Available BACKGROUND Diabetic retinopathy is one of the important microvascular complications of diabetes mellitus of long duration. Alterations in trace metals like magnesium and lipid profile was observed in diabetic retinopathy with hyperglycaemic status. AIM The study was taken up to assess the role of magnesium, lipid profile and glycated haemoglobin in diabetic retinopathy. MATERIALS AND METHODS A total of 80 subjects between 40-65 years were included in the study. Group 1 includes 20 age and sex matched healthy controls. Group 2 includes 30 cases of Diabetes mellitus without retinopathy. Group 3 includes 30 cases of Diabetes mellitus with retinopathy. RESULTS Magnesium was found to be significantly low in the diabetic group with retinopathy. Serum cholesterol and triglycerides were significantly elevated in the diabetic group with retinopathy. Fasting and Postprandial plasma glucose and glycated haemoglobin (HbA1c levels confirmed the glycaemic status of each of the groups. CONCLUSIONS Hypomagnesemia, hypercholesterolaemia, hypertriglyceridemia was observed in diabetic retinopathy along with increased levels of glycated haemoglobin in our study.

  10. Increased adhesion molecules and leukocytes adhesion in human islet endothelial cells by advanced glycation end products%糖基化终末产物上调人胰岛微血管内皮细胞黏附分子的表达和白细胞黏附

    Institute of Scientific and Technical Information of China (English)

    刘虹麟; 许世清; 王在; 彭亮; 房青; 邓婷婷; 游嘉; 娄晋宁; 张文健

    2014-01-01

    目的 研究糖基化终末产物(AGEs)对人胰岛微血管内皮细胞(HIMVEC)黏附分子表达和白细胞黏附的影响.方法 HIMVEC细胞在200 mg/L的AGEs刺激后,用细胞基础的酶联免疫吸附法(ELISA)和Western blotting法检测细胞表面黏附分子的表达;并与BCECF标记的白细胞共培养检测与白细胞的黏附能力.采用实时荧光定量聚合酶链反应(RT-PCR)和Western blotting分别检测HIMVEC细胞上AGEs受体(RAGE)、蛋白激酶Cβ(PKC β)和蛋白激酶A(PKA)的mRNA表达情况.随后给予PKC β抑制剂LY333531或PKA激活剂8-Br-cAMP,观察对HIMVEC黏附分子表达的影响及和白细胞黏附的影响.两组间比较采用t检验进行分析.结果 与对照组相比,AGEs处理后HIMVEC表达P选择素、E选择素和血管细胞黏附分子1(VCAM-1)均上调(分别为1.10 ±0.13比0.64±0.14,0.83 ±0.06比0.47 ±0.05,0.87 ±0.09比0.43±0.07,t =4.93、9.40、7.61,均P<0.05),并且与白细胞的黏附较对照组明显增加(54 ±4比23 ±3,t=12.69,P<0.05).与AGEs组比较,RAGE抗体组P选择素、E选择素和VCAM-1的表达明显降低,组间差异具有统计学意义(t=5.69、6.89、5.43,均P<0.05).RAGE抗体组白细胞黏附明显少于AGEs组(54±4比31 ±4,t=8.22,P<0.05).与对照组相比,AGEs处理HIMVEC 4 h和18h,在mRNA水平和蛋白质水平均检测到RAGE和PKCβ的表达上调,但PKA的表达下调(t=10.94、7.76、21.82、5.85、10.96、11.47,均P<0.05).与AGEs组相比,在AGEs处理时给予PKCβ抑制剂LY333531或PKA激活剂8-Br-cAMP,均可降低HIMVEC上P选择素、E选择素和VCAM-1的表达水平(=7.60、6.60、6.25、11.58、4.08、3.47,均P<0.05),并减少白细胞的黏附(t=7.67、8.89,均P<0.05).结论 AGEs通过RAGE受体上调PKCβ和下调PKA增加HIMVEC上黏附分子的表达,促进白细胞的黏附,可能是糖尿病状态下胰岛中白细胞浸润的机制之一.%Objective To investigate the effect of advanced glycation end products (AGEs) on adhesion

  11. Effects of advanced glycation end products and its receptor on oxidative stress in diabetic wounds%晚期糖基化终末产物与其受体对糖尿病创面氧化应激反应的影响

    Institute of Scientific and Technical Information of China (English)

    牛轶雯; 缪明远; 董炜; 董叫云; 曹晓赞; 陆树良

    2012-01-01

    P<0.01). 结论 异常的氧化应激水平导致糖尿病皮肤具有异常的创伤修复起点,创面愈合过程中AGE-RAGE效应是影响糖尿病创面氧化应激水平的重要因素.%Objective To investigate the accumulation of advanced glycation end products(AGE)and the inflammatory response of skin and wound in diabetic patients,and to analyze their relationship in vitro. Methods Histological staining and immunohistochemical staining was respectively performed on skin and wound tissue specimens collected from 10 patients with Type Ⅱ diabetes mellitus(diabetes group)and 12 non-diabetic patients with skin injury(control group)to observe the arrangement of collagen and the distribution of inflammatory cells,and to determine the expression levels of AGE and its receptor( RAGE).Malondialdehyde(MDA)levels in skin and wound tissue homogenates were assayed by enzyme-linked immunosorbent assay.In vitro,human neutrophils were isolated and treated with RPMI-1640 culture medium or that containing AGE-human serum albumin in the concentration of 0.315,0.625,1.250 mg/mL,and they were identified as normal control(NC)group,low concentration(L)group,moderate concentration (M)group,and high concentration(H)group.Cell viability in each group was determined by MTT colorimetric assay,and the reactive oxygen species(ROS)in cell was measured with 2′,7′-dichlorfluorescein-diacetate.Data were processed with t test. Results Compared with those of skin in control group,collagens of skin tissues in diabetes group atrophied and disorderly arranged.Inflammatory cells in wounds in diabetes group were dispersed,in which collagens arranged loosely and irregularly,as compared with those of wounds in control group.Expression levels of AGE and RAGE of skin in diabetes group were higher than those in control group.In diabetes and control groups,especially in diabetes group,the numbers of RAGE-positive cells in wound tissue were more than those in skin tissue.Large amount of inflammatory

  12. Scopoletin from the flower buds of Magnolia fargesii inhibits protein glycation, aldose reductase, and cataractogenesis ex vivo.

    Science.gov (United States)

    Lee, Jun; Kim, Nan Hee; Nam, Joo Won; Lee, Yun Mi; Jang, Dae Sik; Kim, Young Sook; Nam, Sang Hae; Seo, Eun-Kyoung; Yang, Min Suk; Kim, Jin Sook

    2010-09-01

    Five compounds previously known structures, scopoletin (1), northalifoline (2), stigmast-4-en-3-one (3), tiliroside (4), and oplopanone (5) were obtained from the flower buds of Magnolia fargesii using chromatographic separation methods. The structures of 1-5 were identified by the interpretation of their spectroscopic data including 1D- and 2D-NMR as well as by comparison with reported values. Three compounds 1-3 were found from M. fargesii for the first time in this study. All the isolates (1-5) were subjected to in vitro bioassays to evaluate the inhibitory activity on advanced glycation end products formation and rat lens aldose reductase (RLAR). Compound 1 showed a remarkable inhibitory activity on advanced glycation end products formation with IC(50) value of 2.93 μM (aminoguanidine: 961 μM), and showed a significant RLAR inhibitory activity with IC(50) value of 22.5 μM (3.3-tetramethyleneglutaric acid: 28.7 μM). Compound 4 exhibited potent inhibitory activity against RLAR (IC(50) = 14.9 μM). In the further experiment ex vivo, cataractogenesis of rat lenses induced with xylose was significantly inhibited by compound 1 treatment.

  13. Raman spectroscopy provides a powerful diagnostic tool for accurate determination of albumin glycation.

    Directory of Open Access Journals (Sweden)

    Narahara Chari Dingari

    Full Text Available We present the first demonstration of glycated albumin detection and quantification using Raman spectroscopy without the addition of reagents. Glycated albumin is an important marker for monitoring the long-term glycemic history of diabetics, especially as its concentrations, in contrast to glycated hemoglobin levels, are unaffected by changes in erythrocyte life times. Clinically, glycated albumin concentrations show a strong correlation with the development of serious diabetes complications including nephropathy and retinopathy. In this article, we propose and evaluate the efficacy of Raman spectroscopy for determination of this important analyte. By utilizing the pre-concentration obtained through drop-coating deposition, we show that glycation of albumin leads to subtle, but consistent, changes in vibrational features, which with the help of multivariate classification techniques can be used to discriminate glycated albumin from the unglycated variant with 100% accuracy. Moreover, we demonstrate that the calibration model developed on the glycated albumin spectral dataset shows high predictive power, even at substantially lower concentrations than those typically encountered in clinical practice. In fact, the limit of detection for glycated albumin measurements is calculated to be approximately four times lower than its minimum physiological concentration. Importantly, in relation to the existing detection methods for glycated albumin, the proposed method is also completely reagent-free, requires barely any sample preparation and has the potential for simultaneous determination of glycated hemoglobin levels as well. Given these key advantages, we believe that the proposed approach can provide a uniquely powerful tool for quantification of glycation status of proteins in biopharmaceutical development as well as for glycemic marker determination in routine clinical diagnostics in the future.

  14. Some microbiological aspects of cassava fermentation with emphasis on detoxification of the fermented end-product

    International Nuclear Information System (INIS)

    The search undertaken in this study was for microbial strains able to produce amylase and linamarase simultaneously. A total of 46 organisms (mainly yeasts) were isolated from garri production environments and eighteen more representative isolates were selected for screening. The highest production fo the above enzymes has been found with the yeast strain identified as Saccharomyces sp. Inoculation of this into the cassava mash led to a dramatic reduction of cyanide in the fermenting pulp: 73,4% and 69,2% reduction when compared with controls after 24 and 48 hours of fermentation respectively. The cyanide content of the fermented end-product derived from the inoculated mash was 60,8% and 24% less than in the control after 24 and 48 hours. Preliminary experiments with X-ray radiation of the yeast did not show a sufficient increase in the enzymatic activities of the mutants obtained but only a slight increase in the linamarase production was noticed in mutants derived from irradiation. (author). 27 refs, 9 tabs

  15. Improvement of the nutrient qualities of cassava fermented end-products

    International Nuclear Information System (INIS)

    The yeast strains Saccharomycopsis fibuliger NRRL (Y-2388), Saccharomyces diastaticus NRRL (Y-2416 and Y-4238), Schwaniomyces occidentalis NRRLY-2477 as well as nor-leucine resistant and amylase-overproducing mutants of NRRL-Y-2338 (obtained with the help of NTG-mutagenesis) were used to study their abilities to increase the yield of protein into the cassava fermenting pulp. Their growth kinetics, amylase activity and biomass production initially studied on 2% MYPS medium. S. fibuliger (Y-2388) gave the highest biomass concentration (13,4 g/e) and was found to be superior to other wild strains for protein enrichment of cassava through fermentation. The optimization of the condition for fermentation revealed that 5% w/v of the cassava pulp at pH 6 with an addition of the yeast extract increased the protein content of cassava from 2.8% to 5.6%. The use of amylase overproducing mutants of S. fibuliger Y-2388 inoculated singly or in combination with others did not promote the enrichment of cassava, whereas nor-leucine resistant mutants considerable increased the protein content in the cassava pulp and no supplementation of the pulp with any nutrients is required. Hence, both S. fibuligera Y-2388 wild and its nor-leucine resistant mutant should be considered as a potential inocula with respect to protein enrichment of the cassava fermented end-product. (author). 3 figs, 9 tabs

  16. 胃生长素对晚期糖基化终产物致人脐静脉内皮细胞损伤的影响%Effect of ghrelin on injury of human umbilical vein endothelial cells induced by advanced glycation end products

    Institute of Scientific and Technical Information of China (English)

    李鹏杰; 项莹; 刘莹

    2015-01-01

    Objective To explore the effect of ghrelin on the injury of human umbilical vein endothelial cells (HUVECs) induced by advanced glycation end products (AGE).Methods The HUVECs were isolated and cultured in vitro,exposed to AGE-bovine serum albumin (BSA) with a terminal concentration of 200 mg/L for 24 or 48h with or without pretreatment with ghrelin for 24 h.The cells were divided into serum free group,different concentrations of ghrelin group (0.01,0.1,1 and 10 μmol/L),different concentrations of ghrelin (0.01,0.1,1 and 10 μmol/L) + AGE-BSA group,and AGE-BSA group;48 h after treatment with AGE-BSA,the cell viabilities were measured by thiazolyl blue assays.The cells were divided into serum free group,different concentrations of ghrelin (0.01,0.1,1 and 10 μmol/L) + AGE-BSA group,and AGE-BSA group.48 h after treatment with AGE-BSA,the cell apoptosis was measured by Annexin V-FITC/PI binding assays.The cells were divided into serum free group,AGE-BSA group and ghrelin (1 μmol/L) + AGE-BSA group.24 h after treatment with AGE-BSA,the cell ultrastructure was observed by electron microscopy.The cells were divided into serum free group,ghrelin(1 μmol/L) group,AGE-BSA group and ghrelin(1 μmol/L) + AGE-BSA group;the level of reactive oxygen species (ROS) in cells was measured.Results In different concentrations of ghrelin group,ghrelin promoted cell proliferation in a dose-dependent manner,with remarkable differences of viability between 0.1,1,10 μmol/L ghrelin group and serum free group [(109 ± 18) %,(113 ± 15) %,(115 ± 14) % vs (100 ± 11) %,all P < 0.05].The reduction of cell viability induced by AGE-BSA was inhibited by ghrelin pretreatment in a dose-dependent manner,with significant differences of viability between 1,10 μmol/L ghrelin + AGE-BSA group and AGE-BSA group [(87 ± 18) %,(97 ± 19) %,vs (45 ± 10) %,P < 0.05].The quantity of apoptosis cells was significantly inhibited by 0.1,1,10 μmol/L ghrelin pretreatment in a dose

  17. Roles of advanced glycation end products and its receptor on the fetal brain injury in pregnant rats with gestational diabetes mellitus%晚期糖基化终末产物及其受体在妊娠期糖尿病孕鼠的子鼠脑损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    罗淑静; 杨慧霞

    2012-01-01

    Objective To study the roles of advanced glycation end products and its receptor on fetal brain injury of gestational diabetes mellitus (GDM) rats.Methods Twenty one adult pregnant Wistar rats were administered streptozotocin (STZ) intraperitoneally to induce GDM rats model.The fourteen pregnant rats were divided into two groups according to the fasting glucose on the 3rd day of pregnancy:severe GDM group with the fasting glucose > 16.7 mmol/L and mild GDM group with the fasting glucose between 6.7 - 16.7 mmol/L Another seven pregnant rats were chosen as the severe GDM and intervention with micronutrient group,receiving gavage with micronutrient during the whole pregnancy.Five control rats received the same volume of citric acid buffer.All the pregnant rats were tested fasting glucose from the tailvein and their weight on the pregnant day 3,13 and 19.Maternal serum levels of AGE were measured by ELISA and RAGE levels in the embryonic brain tissues were tested by immunohistochemistry.Results ( 1 ) There was no statistically significant difference of pre-pregnancy fasting glucose level among all groups (P > 0.05 ).The fasting glucose levels on the 3rd day and the mean fasting glucouse level of pregnancy in the severe GDM group and the severe GDM and intervention with micronutrient group were higher than those of the control group ( P <0.05 ).And there was no significant difference between the severe GDM group and the severe GDM and intervention with micronutrient group (P >0.05 ).(2)The serum AGE levels in the severe GDM group and the mild GDM group were( 1037 + 38) ng/L and( 880 ± 34) ng/L respectively,with no significant difference ( P > 0.05 ).The serum AGE levels in the control group and the severe GDM and intervention with micronutrient group were (857 ± 32 ) ng/L and (988 ± 37 ) ng/L,and the difference was statistically significant ( P < 0.05 ).The serum AGE levels in the severe GDM and intervention with micronutrient group and in the mild GDM

  18. Kinetics of fatty acid binding ability of glycated human serum albumin

    Indian Academy of Sciences (India)

    Eiji Yamazaki; Minoru Inagaki; Osamu Kurita; Tetsuji Inoue

    2005-09-01

    Kinetics of fatty acid binding ability of glycated human serum albumin (HSA) were investigated by fluorescent displacement technique with 1-anilino-8-naphtharene sulphonic acid (ANS method), and photometric detection of nonesterified-fatty-acid (NEFA method). Changing of binding affinities of glycated HSA toward oleic acid, linoleic acid, lauric acid, and caproic acid, were not observed by the ANS method. However, decreases of binding capacities after 55 days glycation were confirmed by the NEFA method in comparison to control HSA. The decrease in binding affinities was: oleic acid (84%), linoleic acid (84%), lauric acid (87%), and caproic acid (90%), respectively. The decreases were consistent with decrease of the intact lysine residues in glycated HSA. The present observation indicates that HSA promptly loses its binding ability to fatty acid as soon as the lysine residues at fatty acid binding sites are glycated.

  19. Glycation of high-density lipoprotein in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    SUN Jia-teng; SHEN Ying; L(U) An-kang; LU Lin; SHEN Wei-feng

    2013-01-01

    Objective To evaluate whether glycation of high-density lipoprotein (HDL) increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property.Data sources Data cited in this review were obtained mainly from Pubmed and Medline in English from 2000 to 2013,with keywords "glycation","HDL",and "atherosclerosis".Study selection Articles regarding glycation of HDL and its role in atherogenesis in both humans and experimental animal models were identified,retrieved and reviewed.Results Glycation alters the structure of HDL and its associated enzymes,resulting in an impairment of atheroprotective functionality and increased risks for cardiovascular events in type 2 diabetic patients.Conclusion Glycation of HDL exerts a deleterious effect on the development of cardiovascular complications in diabetes.

  20. Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE patients: glycated-histones as likely trigger for SLE?

    Science.gov (United States)

    Alam, Sana; Arif, Zarina; Alam, Khursheed

    2015-02-01

    Histones are the most abundant proteins associated with genomic DNA. Recent observations show that histones are quite susceptible to non-enzymatic glycation which results in the generation of free radicals causing structural perturbations. In this study, our aim is to define the role of deoxyribose-modified H2A histone in SLE initiation/progression. Glycation reaction was carried out by incubating H2A histone with 10 mM deoxyribose for 21 days at 37 °C. Structural changes in glycated-H2A were studied by various physico-chemical techniques. The antigen-antibody interaction was studied by direct binding, inhibition ELISA and mobility shift assay. Deoxyribose-modified-H2A histone showed increased hyperchromicity and increased fluorescence intensity. CD results demonstrated almost 50% loss in alpha helix conformation as a consequence of glycation. This was supported by an increase in Tm value vis-à-vis thermal stability. Glycated-H2A showed cross linking in SDS-PAGE. SLE sera positive for anti-nDNA autoantibodies showed preference for deoxyribose-modified-H2A histone compared to native H2A histone or native DNA. Inhibition ELISA supported the above findings. Band shift assay further reiterated the preferential recognition of glycated-H2A over native H2A by SLE IgG autoantibodies. Deoxyribose-modified-H2A histone exhibited damage as revealed by various physico-chemical studies. Glycation of H2A has resulted in the generation of neo-epitopes on H2A histone, which are preferably bound by SLE anti-nDNA autoantibodies. It implies that deoxyribose-modified-H2A may trigger immune response resulting in the generation of anti-glycated H2A antibodies with DNA cross reacting properties.

  1. Anti-Glycation Effects of Pomegranate (Punica granatum L.) Fruit Extract and Its Components in Vivo and in Vitro.

    Science.gov (United States)

    Kumagai, Yuya; Nakatani, Sachie; Onodera, Hideaki; Nagatomo, Akifumi; Nishida, Norihisa; Matsuura, Yoichi; Kobata, Kenji; Wada, Masahiro

    2015-09-01

    Accumulation of advanced glycation end products (AGEs) leads to various diseases such as diabetic complications and arteriosclerosis. In this study, we examined the effect of pomegranate fruit extract (PFE) and its constituent polyphenols on AGE formation in vivo and in vitro. PFE, fed with a high-fat and high-sucrose (HFS) diet to KK-A(y) mice, significantly reduced glycation products such as glycoalbumin (22.0 ± 2.4%), hemoglobin A1c (5.84 ± 0.23%), and serum AGEs (8.22 ± 0.17 μg/mL), as compared to a control HFS group (30.6 ± 2.6%, 7.45 ± 0.12%, and 9.55 ± 0.17 μg/mL, respectively, P < 0.05). In antiglycation assays, PFE, punicalin, punicalagin, ellagic acid, and gallic acid suppressed the formation of AGEs from bovine serum albumin and sugars. In this study, we discuss the mechanism of the antiglycation effects of PFE and its components in vivo and in vitro. PMID:26242637

  2. Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2013-01-01

    Full Text Available Advanced glycation end products (AGEs might play a pathophysiological role in the development of diabetes and its complications. AGEs negatively affect pancreatic beta-cell function and the expression of transcriptional factors regulating insulin gene. Glucagon-like peptide-1 (GLP-1, an incretin hormone that regulates glucose homeostasis, might counteract the harmful effects of AGEs on the beta cells in culture. The aim of this study was to identify the intracellular mechanisms underlying GLP-1-mediated protection from AGE-induced detrimental activities in pancreatic beta cells. HIT-T15 cells were cultured for 5 days with glycated serum (GS, consisting in a pool of AGEs, in the presence or absence of 10 nmol/L GLP-1. After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2, glutathione reductase, PDX-1, and MafA. Then, we investigated proinsulin production. The results showed that GS increased oxidative stress, reduced protein expression of all investigated factors through proteasome activation, and decreased proinsulin content. Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. Coincubation with GLP-1 reversed these GS-mediated detrimental effects. In conclusion, GLP-1, protecting cells against oxidants, triggers protective intercellular pathways in HIT-T15 cells exposed to GS.

  3. Antioxidant and anti-glycation activities correlates with phenolic composition of tropical medicinal herbs

    Institute of Scientific and Technical Information of China (English)

    JS Ramkissoon; MF Mahomoodally; N Ahmed; AH Subratty

    2013-01-01

    Objective: To determine the contribution of total phenolic content (TPC) in glycation inhibitory activity of common tropical medicinal food and spices with potential antioxidative properties. Methods: In vitro glucose-bovine serum albumin (BSA) assay was used. Ethanolic extracts of ten common household condiments/herbs (Allium sativum, Zingiber officinale, Thymus vulgaris, Petroselinum crispum, Murraya koenigii Spreng, Mentha piperita L., Curcuma longa L., Allium cepa L., Allium fistulosum and Coriandrum sativum L.) were evaluated for antioxidative activity by 2,2-diphenyl-2-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) and the TPC, flavonoid and tannins content were determined. Results: Findings showed good correlation between TPC/DPPH (r= 0.8), TPC/FRAP (r= 0.8), TPC/Anti-glycation (r=0.9), DPPH/Anti-glycation (r= 0.6), FRAP/Anti-glycation (r = 0.9), Flavonoid/Anti-glycation (r= 0.7) and Tannins/Anti-glycation (r = 0.8) and relatively fair correlation for TPC/Flavonoids (r = 0.5) and TPC/Tannins (r =0.5). Results imply that these plants are potential sources of natural antioxidants which have free radical scavenging activity and might be used for reducing oxidative stress. Conclusions: The positive glycation inhibitory and antioxidative activities of these tropical herbs suggest a possible role in targeting ageing, diabetic complications and oxidative stress related diseases.

  4. Effect of glycation of albumin on its renal clearance in normal and diabetic rats

    International Nuclear Information System (INIS)

    Two independent techniques have been used to study the renal clearances of nonenzymatically glycated albumin and nonglycated albumin in normal and streptozotocin-induced diabetic rats, 16 to 24 weeks after the onset of diabetes. In the first technique, serum and urinary endogenous glycated and nonglycated albumin were separated using m-aminophenylboronate affinity chromatography and subsequently quantified by radioimmunoassay. Endogenous glycated albumin was cleared approximately twofold faster than nonglycated albumin in normal and diabetic rats. However, no difference was observed in the glycated albumin/nonglycated albumin clearance ratios (Cga/Calb) in normal and diabetic rats, respectively (2.18 +/- 0.39 vs 1.83 +/- 0.22, P greater than 0.05). The second technique measured the renal clearance of injected 125I-labelled glycated albumin and 125I-labelled albumin. The endogenous results were supported by the finding that 125I-labelled glycated albumin was cleared more rapidly than 125I-labelled albumin in normal (P less than 0.01) and diabetic (P less than 0.05) rats. The Cga/Calb ratio calculated for the radiolabelled albumins was 1.4 and 2.0 in normal and diabetic rats, respectively. This evidence suggests that nonenzymatic glycation of albumin increases its renal clearance to a similar degree in normal and diabetic rats

  5. The S100B/RAGE Axis in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Estelle Leclerc

    2010-01-01

    Full Text Available Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (A, the Advanced Glycation Endproducts (AGEs, or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.

  6. The skin autofluorescence reflects the posttranslational glycation grade of the matrix protein collagen.

    Science.gov (United States)

    Jacobs, Kathleen; Navarrete Santos, Alexander; Simm, Andreas; Silber, Rolf-Edgar; Hofmann, Britt

    2014-10-01

    Advanced glycation end products (AGEs) seem to be involved in ageing as well as in the development of cardiovascular diseases. Accumulation of AGEs contribute to tissue stiffness and organ dysfunction by crosslinking extracellular matrix proteins like collagen. We aimed to assess whether AGE-modified cardiac tissue collagen and AGE related skin autofluorescence may reflect the cardiac function and have a prognostic value for the outcome of coronary artery bypass surgery patients. Therefore, AGE-modifications in collagen from 72 male patients undergoing isolated coronary artery bypass graft (CABG) surgery were analyzed. Collagen fractions were isolated from the right atrial auricle and the residual bypass graft material (saphenous vein) of these patients and quantified by 4-hydroxyproline assay. AGE modifications were determined by the AGE intrinsic fluorescence (excitation 360nm/emission 440nm). The skin autofluorescence (sAF) as a non-invasive parameter was measured using the AGE reader. The non-extractable collagen contained the highest amounts of AGEs and positively correlates with the patients age (p=0.0001), blood glucose level (p=0.002), HbA1c level (p=0.01) and sAF (p=0.008). The right atrial auricle collagen showed significantly more modifications compared to vein graft material of the same patient (p=0,001). Skin autofluorescence positively correlates with AGE content in cardiac tissue (p=0.01) and therefore could be used as a predictor of tissue stiffness in patients with coronary heart disease.

  7. The skin autofluorescence reflects the posttranslational glycation grade of the matrix protein collagen.

    Science.gov (United States)

    Jacobs, Kathleen; Navarrete Santos, Alexander; Simm, Andreas; Silber, Rolf-Edgar; Hofmann, Britt

    2014-10-01

    Advanced glycation end products (AGEs) seem to be involved in ageing as well as in the development of cardiovascular diseases. Accumulation of AGEs contribute to tissue stiffness and organ dysfunction by crosslinking extracellular matrix proteins like collagen. We aimed to assess whether AGE-modified cardiac tissue collagen and AGE related skin autofluorescence may reflect the cardiac function and have a prognostic value for the outcome of coronary artery bypass surgery patients. Therefore, AGE-modifications in collagen from 72 male patients undergoing isolated coronary artery bypass graft (CABG) surgery were analyzed. Collagen fractions were isolated from the right atrial auricle and the residual bypass graft material (saphenous vein) of these patients and quantified by 4-hydroxyproline assay. AGE modifications were determined by the AGE intrinsic fluorescence (excitation 360nm/emission 440nm). The skin autofluorescence (sAF) as a non-invasive parameter was measured using the AGE reader. The non-extractable collagen contained the highest amounts of AGEs and positively correlates with the patients age (p=0.0001), blood glucose level (p=0.002), HbA1c level (p=0.01) and sAF (p=0.008). The right atrial auricle collagen showed significantly more modifications compared to vein graft material of the same patient (p=0,001). Skin autofluorescence positively correlates with AGE content in cardiac tissue (p=0.01) and therefore could be used as a predictor of tissue stiffness in patients with coronary heart disease. PMID:26461346

  8. Evidence that L-Arginine inhibits glycation of human serum albumin (HSA) in vitro

    International Nuclear Information System (INIS)

    Previous work by Brownlee has shown that glycation of bovine serum albumin can be reduced in the presence of aminoguanidine (AG). Presumably, the guanidinium group on AG interferes with further rearrangement of amadori products to advanced glycosylated end products (AGE). Since L-arginine (ARG) also contains a guanidinium group, its ability to inhibit the formation of AGE products was investigated. HSA was incubated at 37 degrees C in the presence or absence of glucose; with glucose and fructose; or with sugars in the presence or absence of ARG or AG. A tracer amount of U-14C-glucose was added to each tube containing sugars. Protein bound glucose was separated from unreacted glucose by gel filtration. Radioactivity, total protein, fluorescence, and glucose concentration were measured. Preliminary data show enhanced binding of 14C-glucose to HSA with fructose at all time points. A 30-40% decrease in 14C-glucose incorporation was observed when ARG or AG as present. ARG and AG were equally effective in inhibiting incorporation of 14C-glucose. FPLC analysis is in progress to determine the type and degree of HSA crosslinking during the 2 week incubation period

  9. The combination of radiotherapy and immunotherapy using glycated chitosan as an immunological stimulant

    Science.gov (United States)

    Chang, Chun-Yuan; Leu, Jyh-Der; Wang, Chung-Yi; Chen, Wei R.; Lee, Yi-Jang

    2015-03-01

    Immunotherapy has been reported to effectively treat various cancers. In addition, scientists are dedicated in finding whether the combination of radiotherapy and immunotherapy can efficiently suppress cancer progression and recurrence. Although radiotherapy has been widely used for breast cancer, better strategies to overcome the latestage breast cancer remains explored. The glycated chitosan (GC), a novel immunological stimulant, was demonstrated to trigger local immune response facilitating the enhancement of radiosensitivity. Our previous study also revealed that the cell mortality and invasive ability were decreased under GC treatment, but the underlying mechanism remains unclear. In this study, we used 4T1-3R-L, a derived murine breast cancer cell line from the spontaneous metastasized liver lesion. We combined ionizing radiation with GC to treat 4T1-3R-L and found the expression of DNA damage-related genes such as gamma-H2AX was more than radiation alone In addition, the cell cycle distribution and colony forming assay showed an increased sub-G1 population and decreased cell survival rate after IR combined GC treatment. Taken together, we sought to elucidate the underlying mechanism by the investigation of DNA damage repair process when IR combined with GC, and to explore another advantage of GC to aid other cancer treatments. Based on our most updated results, the GC treatment is able to effectively increase the radiosensitivity through an immune-responsive signaling transduction, indicating that GC could be a valuable therapeutic strategy for treating against advanced breast cancers.

  10. Glycation: the angiogenic paradox in aging and age-related disorders and diseases.

    Science.gov (United States)

    Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E

    2014-05-01

    Angiogenesis is generally a quiescent process which, however, may be modified by different physiological and pathological conditions. The "angiogenic paradox" has been described in diabetes because this disease impairs the angiogenic response in a manner that differs depending on the organs involved and disease evolution. Aging is also associated with pro- and antiangiogenic processes. Glycation, the post-translational modification of proteins, increases with aging and the progression of diabetes. The effect of glycation on angiogenesis depends on the type of glycated proteins and cells involved. This complex link could be responsible for the "angiogenic paradox" in aging and age-related disorders and diseases. Using diabetes as a model, the present work has attempted to review the age-related angiogenic paradox, in particular the effects of glycation on angiogenesis during aging.

  11. Aptamer-based surface plasmon resonance sensing of glycated human blood proteins

    Science.gov (United States)

    Reaver, Nathan G. F.; Zheng, Rui; Kim, Dong-Shik; Cameron, Brent D.

    2013-02-01

    The concentration ratio of glycated to non-glycated forms of various blood proteins can be used as a diagnostic measure in diabetes to determine a history of glycemic compliance. Depending on a protein's half-life in blood, compliance can be assessed from a few days to several months in the past, which can then be used to provide additional therapeutic guidance. Current glycated protein detection methods are limited in their ability to measure multiple proteins, and are susceptible to interference from other blood pathologies. In this study, we developed and characterized DNA aptamers for use in Surface Plasmon Resonance (SPR) sensors to assess the blood protein hemoglobin. The aptamers were developed by way of a modified Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process which selects DNA sequences that have a high binding affinity to a specific protein. DNA products resulting from this process are sequenced and identified aptamers are then synthesized. The SELEX process was performed to produce aptamers for a glycated form of hemoglobin. Equilibrium dissociation constants for the binding of the identified aptamer to glycated hemoglobin, hemoglobin, and fibrinogen were calculated from fitted Langmuir isotherms obtained through SPR. These constants were determined to be 94 nM, 147 nM, and 244 nM respectively. This aptamer can potentially be used to create a SPR aptamer based biosensor for detection of glycated hemoglobin, a technology that has the potential to deliver low-cost and immediate glycemic compliance assessment in either a clinical or home setting.

  12. Fluorescence lifetime measurements of native and glycated human serum albumin and bovine serum albumin

    Science.gov (United States)

    Joshi, Narahari V.; Joshi, Virgina O. d.; Contreras, Silvia; Gil, Herminia; Medina, Honorio; Siemiarczuk, Aleksander

    1999-05-01

    Nonenzymatic glycation, also known as Maillard reaction, plays an important role in the secondary complications of the diabetic pathology and aging, therefore, human serum albumin (HSA) and bovine serum albumin (BSA) were glycated by a conventional method in our laboratory using glucose as the glycating agent. Fluorescence lifetime measurements were carried out with a laser strobe fluorometer equipped with a nitrogen/dye laser and a frequency doubler as a pulsed excitation source. The samples were excited at 295 nm and the emission spectra were recorded at 345 nm. The obtained decay curves were tried for double and triple exponential functions. It has been found that the shorter lifetime increases for glycated proteins as compared with that of the native ones. For example, in the case of glycated BSA the lifetime increased from 1.36 ns to 2.30 ns. Similarly, for HSA, the lifetime increases from 1.58 ns to 2.26 ns. Meanwhile, the longer lifetime changed very slightly for both proteins (from 6.52 ns to 6.72 ns). The increase in the lifetime can be associated with the environmental effect; originated from the attachment of glucose to some lysine residues. A good example is Trp 214 which is in the cage of Lys 225, Lys 212, Lys 233, Lys 205, Lys 500, Lys 199 and Lys 195. If fluorescence lifetime technique is calibrated and properly used it could be employed for assessing glycation of proteins.

  13. Non-enzymatic glycation of type I collagen diminishes collagen-proteoglycan binding and weakens cell adhesion

    OpenAIRE

    Reigle, Kristin L.; Di Lullo, Gloria; Turner, Kevin R.; Last, Jerold A; Chervoneva, Inna; Birk, David E.; Funderburgh, James L.; Elrod, Elizabeth; Markus W. Germann; Surber, Charles; Sanderson, Ralph D.; San Antonio, James D.

    2008-01-01

    Non-enzymatic glycation of type I collagen occurs in aging and diabetes, and may affect collagen solubility, charge, polymerization, and intermolecular interactions. Proteoglycans1(PGs) bind type I collagen and are proposed to regulate fibril assembly, function, and cell-collagen interactions. Moreover, on the collagen fibril a keratan sulfate (KS) PG binding region overlaps with preferred collagen glycation sites. Thus, we examined the effect of collagen modified by simple glycation on PG-co...

  14. Effect of atorvastatin on advanced glycation end products induced monocyte chemoattractant protein-1 expression in cultured human endothelial cells%阿托伐他汀对晚期糖基化终末产物诱导的人内皮细胞单核细胞趋化蛋白-1mRNA表达影响及其机制的实验研究

    Institute of Scientific and Technical Information of China (English)

    徐尚华; 王科峰; 许昌声; 谢良地

    2011-01-01

    Objective To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1(MCP-1) expression in human umbilical vein endothelial cells(HUVECs)and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB(NF-κB).Methods Grouping: (1)Blank control group;(2)BSA group;(3)AGE group:cells were incubated with different concentrations of AGE(10-4,10-3, 10-2 and 10-1g/L)for 24 hours; (4)AGE+Atorvastatin group: cells were incubated with different concentrations of atorvastatin(0.1,1,10 μmol/L)for 1 hour,then incubated with AGE (10-1 g/L) for 24 hours; (5)PPAR-γ agonist(15 d-PGJ2)group: cells were incubated with 15 d-PGJ2(10 μmol/L)for 1 hour,then incubated with AGE (10-1g/L) for 24 hours;(6)PPAR-γ inhibitor(GW9662)group:cells were incubated with GW9662(5000 nmol/L)for 1 hour,then incubated with atorvastatin (1 μmol/L)and AGE (10-1g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein;RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ;Western blot was performed to detect NF-κB p65 protein.Results (1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE(10-1g/L)significantly downregulated the expression of PPAR-γ mRNA(0.22±0.08 vs. 0.69±0.09, P<0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78±0.06 vs. 0.31±0.01,P<0.01) and nonphospho-NF-κB p65 protein (1.61±0.16 vs. 0.59±0.14,P<0.01) comparaed with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21±0.01 vs. 0.78±0.06, P<0.01),nonphospho-NF-κB p65 protein (0.67±0.14 vs. 1.61±0.16,P<0.01)and MCP-1 mRNA (0.17±0.02 vs. 0.93±0.12, P<0.01)compared with AGE(10-1g/L)group. (4) PPAR

  15. Activated carbons from end-products of tree nut and tree fruit production as sorbents for removing methyl bromide in ventilation effluent from postharvest chamber fumigation

    Science.gov (United States)

    End-products of tree nuts and tree fruits grown in California, USA were evaluated for the ability to remove methyl bromide from the ventilation effluent of postharvest chamber fumigations. Activated carbon sorbents from walnut and almond shells as well as peach and prune pits were prepared using dif...

  16. Long-term cathode performance and the microbial communities that develop in microbial fuel cells fed different fermentation endproducts

    KAUST Repository

    Kiely, Patrick D.

    2011-01-01

    To better understand how cathode performance and substrates affected communities that evolved in these reactors over long periods of time, microbial fuel cells were operated for more than 1year with individual endproducts of lignocellulose fermentation (acetic acid, formic acid, lactic acid, succinic acid, or ethanol). Large variations in reactor performance were primarily due to the specific substrates, with power densities ranging from 835±21 to 62±1mW/m3. Cathodes performance degraded over time, as shown by an increase in power of up to 26% when the cathode biofilm was removed, and 118% using new cathodes. Communities that developed on the anodes included exoelectrogenic families, such as Rhodobacteraceae, Geobacteraceae, and Peptococcaceae, with the Deltaproteobacteria dominating most reactors. Pelobacter propionicus was the predominant member in reactors fed acetic acid, and it was abundant in several other MFCs. These results provide valuable insights into the effects of long-term MFC operation on reactor performance. © 2010 Elsevier Ltd.

  17. Comparable application of the OCT and Abbe refractometers for measurements of glycated hemoglobin portion in blood

    Science.gov (United States)

    Zhernovaya, Olga S.; Tuchin, Valery V.; Wang, Ruikang K.

    2006-02-01

    It is known that glucose interacts with plasma proteins and hemoglobin in erythrocytes. Glycated (glycosylated) hemoglobin is the result of an irreversible non-enzymatic fixation of glucose on the beta chain of hemoglobin A. The amount of glycated hemoglobin depends on blood glucose concentration and reflects the mean glycemia of about the previous 2-3 months. Glycated hemoglobin is a useful marker for long-term glucose control in diabetic patients. Therefore, the search of quick and high sensitive methods for measurement of glycated hemoglobin portion in blood is important. This study is focused on the determination of refractive index of hemoglobin solution at different glucose concentrations. Measurements were performed using Abbe refractometer at 589 nm and optical coherence tomography (OCT) at 820 nm. The different amount of glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) was added to hemoglobin solution. Theoretical values of refractive index of hemoglobin solutions with glucose were calculated supposing non-interacting hemoglobin and glucose molecules. There is a difference between measured and calculated values of refractive index. This difference is due to glucose binding to hemoglobin. It is shown that the refractive index measurements can be applied for the evaluation of glycated hemoglobin amount.

  18. The Effect of Turmeric , Cardamom and Ginger on in vitro Albumin Glycation

    Directory of Open Access Journals (Sweden)

    N. Sheikh

    2004-01-01

    Full Text Available Diabetes mellitus is one of the most common disease in the world that imposes a tremendous health and societal burden whether that burden is measured in terms of sickness , use of health systems resources or costs. Hyperglycemia is the most important clinical sign of diabetes leading to glycation of the various proteins in the body that leads to change in their nature , structure and biochemical activity. One of the probable methods in the treatment of diabetes mellitus is decrease or inhibition of this reaction. It seems that Turmeric , Cardamom and Ginger are useful for this purpose. The main goal of this research is to determine the effect of above agents on in vitro albumin glycation. In the presence of various concentration of these agents , albumin was glycated and evaluated using TBA method. Results showed that these food additives have inhibitory effects on albumin glycation reaction with the concentraction of 1 g/dl , 0.2 g/dl and 0.1 g/dl. Among these agents , Ginger had the most inhibitory effect (78% with the concentration of 1 g/dl. The sequence of effect is : Ginger > Cardamom > Turmeric These findings showed that these agents decrease albumin glycation reaction.

  19. The effects of baicalin on inhibiting brain aging, glycation-oxidative stress and insulin resistance in D-galactose-induced aging rats%黄芩苷对D半乳糖诱导衰老大鼠拮抗脑老化糖基化氧化应激及胰岛素抵抗作用

    Institute of Scientific and Technical Information of China (English)

    钟成; 潘竞锵; 吕俊华; 郑琳颖; 李博萍

    2012-01-01

    models were randomly divide into 5groups ( 15 rats for each goup ):model control,metformin ( Met,150 mg·kg-1 ),and pimagedine ( PG,150 mg·kg-1 ),Bai high dose group( 300 mg·kg-1 )and low dose group ( 150 mg·kg-1 ); then ip D-gal and different drugs or distilled water ip-treated qd for 42 days.In the end of the experiment,the contents of fasting blood glucose ( FBG ),fruetosamine ( FRA ),glycosylated hemoglobin ( HbAIc ),advanced glycation end-products ( AGEs ),insulin,and malondialdehyde ( MDA ) were analyzed,the activity of aldose reductase ( AR ) and superoxide dismutase ( SOD ) were determined,insulin sensitivity index ( ISI ) was counted and spatial seeking ability by Morris water maze test was selected.Results As compared with blank control,the concentration of FBG,FRA,HbA lc,AGEs,insulin and MDA increased ( P< 0.01 ),SOD activity declined ( P< 0.01 ),AR activity enhanced ( P< 0.01 ),ISI reduced ( P< 0.01 ),and spatial seeking ability significantly declined in the D-gat-induced rats; as compared with the D-gal-induced aging rats,the contents of FBG,FRA,HbAIc,AGEs and insulin were reduced,AR activity was inhibited,SOD activity was elevated,and spatial seeking ability was significantly increased by using Met,PG,and Bai at high or low dose ( P < 0.05 or P < 0.01 ).Conclusions Baicalin can antagonize insulin resistance,improve insulin sensitivity,inhibit formation of glycation products-oxidative stress and activity of rate-limiting enzyme AR in polyoi pathway,suppress inflamnatory reaction,and improve spatial seeking ability in D-gal-induced aging rats.The effects of baicalin reveals a dose-effect relationship.

  20. Antimicrobial properties of nisin after glycation with lactose, maltodextrin and dextran and the thyme oil emulsions prepared thereof.

    Science.gov (United States)

    Chen, Huaiqiong; Davidson, P Michael; Zhong, Qixin

    2014-11-17

    To clarify the reported conflicting antimicrobial activities of nisin after glycation, nisin was glycated with lactose, maltodextrin, and dextran at 70 °C and 50% relative humidity for 1-24 h. Nisin before and after glycation was studied for the first time to prepare thyme oil emulsions. The activity of glycated nisin and the thyme oil emulsions was tested in both tryptic soy broth (TSB) and 2% reduced fat milk. Results showed that nisin glycated with a smaller saccharide for a longer duration had a higher degree of glycation and the reduced number of positive charges lowered its antibacterial activity. The emulsified thyme oil had an additive effect with either glycated or native nisin against Listeria monocytogenes Scott A and Bacillus subtilis in TSB and 2% reduced fat milk. However, emulsions were less effective against L. monocytogenes Scott A in milk than same units of native nisin and same concentration of free thyme oil, likely due to the reduced availability of thymol and carvacrol, the main components of thyme oil. These results showed that glycation of nisin cannot broaden its antimicrobial activity and nisin is not a good compound to prepare emulsions of essential oils.

  1. Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats

    NARCIS (Netherlands)

    Waanders, F; Greven, WL; Baynes, JW; Thorpe, [No Value; Kramer, AB; Nagai, R; Sakata, N; van Goor, H; Navis, G

    2005-01-01

    Background. Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether

  2. Elevation of cartilage AGEs does not accelerate initiation of canine experimental osteoarthritis upon mild surgical damage

    NARCIS (Netherlands)

    Vos, P.A.J.M.; Degroot, J.; Barten-Van Rijbroek, A.D.; Zuurmond, A.-M.; Bijlsma, J.W.J.; Mastbergen, S.C.; Lafeber, F.P.J.G.

    2012-01-01

    Osteoarthritis is a highly prevalent disease, age being the main risk factor. The age-related accumulation of advanced-glycation-endproducts (AGEs) adversely affects the mechanical and biochemical properties of cartilage. The hypothesis that accumulation of cartilage AGEs in combination with surgica

  3. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Toes, R.E.M.; Ronday, H.K.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristi

  4. Skin autofluorescence, a non-invasive marker for AGE accumulation, is associated with the degree of atherosclerosis

    NARCIS (Netherlands)

    den Dekker, Martijn A. M.; Zwiers, Marjan; van den Heuvel, Edwin R.; de Vos, Lisanne C.; Smit, Andries J.; Zeebregts, Clark J.; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Lefrandt, Johan; Mulder, Douwe J.

    2013-01-01

    Introduction: Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with th

  5. Increase in Skin Autofluorescence and Release of Heart-Type Fatty Acid Binding Protein in Plasma Predicts Mortality of Hemodialysis Patients

    NARCIS (Netherlands)

    Arsov, Stefan; Trajceska, Lada; van Oeveren, Wim; Smit, Andries J.; Dzekova, Pavlina; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Graaff, Reindert

    2013-01-01

    Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (DAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients.

  6. Elevated skin autofluorescence is strongly associated with foot ulcers in patients with diabetes : a cross-sectional, observational study of Chinese subjects

    NARCIS (Netherlands)

    Hu, Hang; Han, Chun-mao; Hu, Xin-lei; Ye, Wan-lan; Huang, Wen-juan; Smit, Andries J.

    2012-01-01

    This study was designed to evaluate the association between skin autofluorescence (AF), an indicator of advanced glycation end-products (AGEs), and foot ulcers in subjects with diabetes. In this study, 195 Chinese diabetic subjects were examined. Their feet were examined regardless of whether an ulc

  7. 蛋白の糖化 : メイラード反応を中心にして

    OpenAIRE

    堀川, 博朗; HORIKAWA, Hiroaki

    2004-01-01

    The Maillard reaction is a complex and poorly understood series of reactions between reducing sugars and the primary amino groups of proteins. The resulting advanced glycation end-products (AGEs) and active oxygen species are thought to contribute to the development of diabetic complications and aging. This review describes the basic chemistry of the Maillard reaction.

  8. Time course of specific AGEs during optimised glycaemic control in type 2 diabetes

    NARCIS (Netherlands)

    Mentink, CJAL; Kilhovd, BK; Rondas-Colbers, GJWM; Torjesen, PA; Wolffenbuttel, BHR

    2006-01-01

    Background: Several advanced glycation endproducts (AGEs) are formed in the hyperglycaemic state. Although serum AGEs correlate with average glycaemic control in patients with type 2 diabetes and predict the development of complications, it is not known how serum AGEs change during optimisation of d

  9. Skin Autofluorescence Based Decision Tree in Detection of Impaired Glucose Tolerance and Diabetes

    NARCIS (Netherlands)

    Smit, Andries J.; Smit, Jitske M.; Botterblom, Gijs J.; Mulder, Douwe J.

    2013-01-01

    Aim: Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compare

  10. A novel imaging platform for non-invasive screening of abnormal glucose tolerance.

    Science.gov (United States)

    Jeong, Bosu; Jung, Chang Hee; Lee, Yong-Ho; Shin, Il-Hyung; Kim, Hansuk; Bae, Soo-Jin; Lee, Dae-Sic; Kang, Eun Seok; Kang, Uk; Kim, Jong Jin; Park, Joong-Yeol

    2016-06-01

    Optical measurement of skin auto-fluorescence (SAF), most likely emanating from accumulated advanced glycation end-products (AGEs), has been proposed for the noninvasive diagnosis of glucose intolerance in clinical settings. Here, we developed a novel imaging system with transmission geometry for SAF measurement and compared its diagnostic performance in a Korean population. PMID:27321320

  11. In end stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters of cartilage damage

    NARCIS (Netherlands)

    Vos, P.A.J.M.; Mastbergen, S.C.; Huisman, A.M.; Boer, T.N.de; Groot, J.de; Polak, A.A.; Lafeber, F.P.J.G.

    2012-01-01

    Objectives: Age is the most prominent predisposition for development of osteoarthritis (OA). Age-related changes of articular cartilage are likely to play a role. Advanced glycation endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the biomechanical propertie

  12. Skin color independent assessment of aging using skin autofluorescence

    NARCIS (Netherlands)

    M. Koetsier; E. Nur; H. Chunmao; H.L. Lutgers; T.P. Links; A.J. Smit; G. Rakhorst; R. de Graaff

    2010-01-01

    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 select

  13. Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus.

    Science.gov (United States)

    Wu, Wan-Chen; Ma, Wen-Ya; Wei, Jung-Nan; Yu, Tse-Ya; Lin, Mao-Shin; Shih, Shyang-Rong; Hua, Cyue-Huei; Liao, Ying-Jhu; Chuang, Lee-Ming; Li, Hung-Yuan

    2016-01-01

    In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, pdiet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.

  14. Analysis and Quantitation of Glycated Hemoglobin by Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry

    Science.gov (United States)

    Hattan, Stephen J.; Parker, Kenneth C.; Vestal, Marvin L.; Yang, Jane Y.; Herold, David A.; Duncan, Mark W.

    2016-03-01

    Measurement of glycated hemoglobin is widely used for the diagnosis and monitoring of diabetes mellitus. Matrix assisted laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometry (MS) analysis of patient samples is used to demonstrate a method for quantitation of total glycation on the β-subunit of hemoglobin. The approach is accurate and calibrated with commercially available reference materials. Measurements were linear (R2 > 0.99) across the clinically relevant range of 4% to 20% glycation with coefficients of variation of ≤ 2.5%. Additional and independent measurements of glycation of the α-subunit of hemoglobin are used to validate β-subunit glycation measurements and distinguish hemoglobin variants. Results obtained by MALDI-TOF MS were compared with those obtained in a clinical laboratory using validated HPLC methodology. MALDI-TOF MS sample preparation was minimal and analysis times were rapid making the method an attractive alternative to methodologies currently in practice.

  15. Accumulation of glycation products in. cap alpha. -H pig lens crystallin and its bearing to diabetic cataract genesis

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, P.; Cabezas-Cerrato, J.

    1988-01-01

    The incorporation of /sup 11/C-glucose in native pig crystalline by in vitro incubation was found, after subsequent dialysis, to affect all 5 classes of crystallin separated by Sepharose CL-6B column chromatography. Though the radioactivity of the ..cap alpha..-H fraction was three times greater than that of any of the others, autoradiographs of SDS-PAGE gels showed /sup 11/C-glucose adducts to be present in all soluble protein subunits, without there being any evidence of preferential glycation of the ..cap alpha..-H subunits. The concentration of stable glycation products in the ..cap alpha..-H chromatographic fraction of soluble crystallins is suggested to be due the addition of glycated material to this fraction as result of glycation-induced hyperaggregation, and not because the ..cap alpha..-H subunits were especially susceptible to glycation.

  16. The effect of Cerasus avium stalk extract on albumin glycation reaction

    Directory of Open Access Journals (Sweden)

    Mohadeseh Abdoli

    2014-10-01

    Full Text Available Background: Non-enzymatic glycosylation of proteins is the major cause of diabetic complications. The inhibition of glycation process can reduce complications of diabetes. In the Iranian traditional medicine, the decoction (boiled extraction of Cerasus avium stalk is used as a hypoglycemic agent. The aim of this study was to investigate the in vitro inhibitory effects of decoction and ethanolic and aqueous extracts of Cerasus avium stalk on albumin glycation reaction. Methods: In this experimental study, first, the ethanolic, aqueous and decoction extracts of Cerasus avium stalk were prepared. Then, different concentrations of these extracts were prepared and added to albumin and glucose solutions. Finally, compared to control group that was not treated with any extracts, the albumin glycation rate in the groups treated with various concentrations of extracts was evaluated using TBA (thio-barbituric acid method. Results: The results showed that compared to control group, decoction of Cerasus avium stalk in the concentrations of 20, 10 and 2 mg/dl could reduce albumin glycation to 85.10±1.55, 72.35±1.75 and 51.25±1.22 %, respectively (P>0.001. Moreover, in the concentration of 20 mg/dl, the inhibitory effect of decoction of Cerasus avium stalk on the albumin glycation reaction was higher than those of aqueous (P=0.021 and ethanolic (P=0.009 extracts. Conclusion: The findings showed that the extracs of Cerasus avium stalk, in particular in the decoction form, could significantly reduce the rate of albumin glycation; therefore, it can be used for decreasing diabetes mellitus complications.

  17. Effect of Advanced Glycation End Products on NADPH Oxidase Subunit p22phox Expression and Reactive Oxygen Species Production in Vascular Adventitial Fibroblasts in Rats%晚期糖基化终产物对大鼠血管外膜成纤维细胞中烟酰胺腺嘌呤二核苷酸磷酸氧化酶p22phox亚基及活性氧表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘亚洋; 李鹤; 吴宗贵; 汤锡友

    2012-01-01

    胞内活性氧的产生.%Objective: To investigate the effect of advanced glycation end products (AGE) on NADPH oxidase subunit p22phox expression and reactive oxygen species (ROS) production in vascular adventitial fibroblasts (VAF) in rats.Methods : The isolated VAF of SD rats were cultured with the adherent tissue explants method. ①The effect of AGE-HSA on p22phox mRNA and protein expression were measured by RT-PCR and Western-blot with different concentrations of AGE-HSA at 100 μg/ml, 200 μg/ml,300 μg/ml and Control group respectively. ②The effect of different reagents on AGE-HSA regulating p22phox mRNA and protein expression were conducted as 200 μg/ml AGE-HSA group,200 μg/ml AGE-HSA + anti-RAGE neu- Lralizing anlibody group, and 200 μg/ml AGE-HSA + Candesartan group. ③The effect of differenl reagenls on ROS production in AF were measured by ROS assay kit as 200 μg/ml AGE-HSA group,200 μg/ml AGE-HSA + anti-RAGE neutralizing anlibody group,200 μg/ml AGE-HSA + Apopcin group,and 200 μg/ml AGE-HSA + CandesarLan group.Resulls; (T)Compared wilh ConLrol group, p22phox mRNA and prolein expression were up-regulaled by AGE-HSA in a dose-dependenl manner. ①Compared wilh 200μg/ml AGE-HSA group,p22phox mRNA and prolein expression decreased in 200 μg/ ml AGE-HSA + anli-RAGE neutralizing anlibody group and 200 μg/ml AGE-HSA + Candesarlan group. ③Compared wilh 200 μg/ml AGE-HSA group,the ROS produclion in VAF decreased in 200 μg/ml AGE-HSA + anli-RAGE neutralizing anlibody group,200 μg/ml AGE-HSA + Apopcin group,and 200 μg/ml AGE-HSA + Candesarlan group. All P<0. 05.Conclusion; The mRNA and prolein expression of p22phox,lhe ROS produclion in VAF were up-regulaled by AGE-HSA in rals,and those effecls could be inhibited by RAGE. NADPH oxidase inhibitors and candesarlan can reduce ROS by down-regulating p22phox expression.

  18. 糖基化终末产物对人牙周膜干细胞脂向分化相关基因C/EBPβ、PPAR-γ的影响%The effect of advanced glycation end products on the adipogenic differentiation of human periodontal ligament stem cells and its effect on C/EBPβ,PPAR-γexpression

    Institute of Scientific and Technical Information of China (English)

    邓超; 王云; 柳海; 周嵩琳; 伍燕; 刘琪

    2015-01-01

    Objective:To investigate the effect of advanced giycation end products ( AGEs) on the adipogenic differentiation of hu-man periodontai iigament stem ceiis (HPDLSCs) and detect the C/EBPβ,PPAR-γgene expression.Methods:HPDLSCs were isoiated by iimited diiution of cuiture ceiis for singie ceii cione .The osteogenic differentiation capacity of HPDLSCs was evaiuated by Aiizarin red staining,whiie the adipogenic differentiation capacity of HPDLSCs was evaiuated by oii red staining .HPDLSCs were induced with AGEs.Reai time quantitative reverse transcription poiymerase chain reaction (Reai time PCR) was performed to detect the differences of gene expression between the controi group and experimentai group .Results:After 21 days induction , Aiizarin red staining showed mineraiization noduies were formed .and oii red staining showed iipid dropiets were formed .After AGEs stimuiation , during HPDLSCs adipogenic differentiation ,the formation of iipid dropiets increased in the experimentai group .The expressions of CCAAT enhancer bind-ing protein β( C/EBPβ) and peroxisome proiiferator activated receptors γ( PPAR-γ) in the experimentai group were higher than those in the controi group.The differences were statisticaiiy significant (P<0.05).Conclusions:AGEs can promote the adipogenic differen-tiation capacity of HPDLSCs ,and change the expressions of C/EBPβ,PPAR-γmRNA ieveis.%目的:通过检测CCAAT/增强子结合蛋白β( C/EBPβ)、过氧化物酶体增殖物激活受体γ( PPAR-γ)基因的表达探讨糖基化终末产物(AGEs)对人牙周膜干细胞(HPDLSCs)脂向分化能力的影响. 方法:体外组织块法和有限稀释法克隆化培养人牙周膜干细胞;成骨、成脂诱导人牙周膜细胞,对其进行干细胞鉴定. 分别成脂诱导正常的人牙周膜干细胞和AGEs刺激下的人牙周膜干细胞,油红O染色观测两组细胞脂滴形成情况. 实时定量聚合酶链反应(Reai time PCR)检测成脂诱导后AGEs刺激下C

  19. Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Wan-Chen Wu

    Full Text Available In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c is sometimes measured to determine the need of an oral glucose tolerance test (OGTT. However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001, serum albumin (r = -0.1179, age-adjusted p = 0.001, body mass index (r = -0.24, age-adjusted p<0.001, waist circumference (r = -0.16, age-adjusted p<0.001, and plasma GA (r = 0.999, p<0.001, but was unaffected by diet (p = 0.8. Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT% with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%, but a significant increase in OGTT% (35%. Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes, the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%. In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.

  20. Enrichment and Analysis of Nonenzymatically Glycated Peptides: Boronate Affinity Chromatography Coupled with Electron-Transfer Dissociation Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Tang, Ning; Brock, Jonathan W.; Mottaz, Heather M.; Ames, Jennifer M.; Baynes, John; Smith, Richard D.; Metz, Thomas O.

    2007-06-01

    Non-enzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the development of diabetic complications. However, no effective high-throughput methods exist for identifying proteins containing this low abundance post-translational modification in bottom-up proteomic studies. In this report, phenylboronate affinity chromatography was used in a two-step enrichment scheme to selectively isolate first glycated proteins and then glycated, tryptic peptides from human serum glycated in vitro. Enriched peptides were subsequently analyzed by alternating electron transfer dissociation (ETD) and collision induced dissociation (CID) tandem mass spectrometry. It was observed that ETD fragmentation mode resulted in a significantly higher number of glycated peptide identifications (87.6% of all identified peptides) versus CID mode (17.0% of all identified peptides), when utilizing dual glycation enrichment on both the protein and peptide level. This study illustrates that phenylboronate affinity chromatography coupled with LC-MS/MS with ETD as the fragmentation mode is an efficient approach for analyses of glycated proteins and can have broad applications in studies of diabetes mellitus.

  1. Ascorbic acid glycation of lens proteins produces UVA sensitizers similar to those in human lens

    International Nuclear Information System (INIS)

    Soluble calf lens proteins were extensively glycated during a 4 week incubation with ascorbic acid in the presence of oxygen. Amino acids analysis of the dialyzed proteins removed at weekly intervals showed an increasing loss of lysine, arginine and histidine, consistent with the extensive protein cross-linking observed. Irradiation of the dialyzed samples with UVA light (1.0 kJ/cm2 total illumination through a 338 nm cutoff filter) caused an increasing loss of tryptophan, an additional loss of histidine and the production of micromolar concentrations of hydrogen peroxide. No alteration in amino acid content and no photolytic effects were seen in proteins incubated without ascorbic acid in proteins incubated with glucose for 4 weeks. The rate of hydrogen peroxide formation was linear with each glycated sample with a maximum production of 25 nmol/mg protein illuminated. The possibility that the sensitizer activity was due to an ascorbate-induced oxidation of tryptophan was eliminated by the presence of a heavy metal ion chelator during the incubation and by showing equivalent effects with ascorbate-incubated ribonuclease A, which is devoid of tryptophan. The ascorbate-incubated samples displayed increasing absorbance at wavelengths above 300 nm and increasing fluorescence (340/430) as glycation proceeded. The spectra of the 4 week glycated proteins were identical to those obtained with a solubilized water-insoluble fraction from human lens, which is known to have UVA sensitizer activity. (Author)

  2. Accumulation of advanced glycation end (AGEs products in intensive care patients: an observational, prospective study

    Directory of Open Access Journals (Sweden)

    Rommes Johannes H

    2010-05-01

    Full Text Available Abstract Background Oxidative stress plays an important role in the course and eventual outcome in a majority of patients admitted to the intensive care unit (ICU. Markers to estimate oxidative stress are not readily available in a clinical setting. AGEs accumulation has been merely described in chronic conditions, but can also occur acutely due to oxidative stress. Since AGEs have emerged to be stable end products, these can be a marker of oxidative stress. Skin autofluorescence (AF is a validated marker of tissue content of AGEs. We hypothesized that AGEs accumulate acutely in ICU patients. Methods We performed an observational prospective study in a medical surgical ICU in a university affiliated teaching hospital. All consecutively admitted ICU patients in a 2 month period were included. Skin AF was measured using an AGE reader in 35 consecutive ICU patients > 18 yrs. As a comparison, historical data of a control group (n = 231 were used. These were also used to calculate age-adjusted AF-levels (AFadj. Values are expressed as median and interquartile range [P25-P75]. Differences between groups were tested by non parametric tests. P Results AFadj values were higher in ICU patients (0.33 [0.00 - 0.68] than in controls (-0.07 [-0.29 - 0.24]; P adj were observed between acute or planned admissions, or presence of sepsis, nor was skin AFadj related to severity of disease as estimated by APACHE-II score, length of ICU, hospital stay or mortality. Conclusion Acute AGE accumulation in ICU patients was shown in this study, although group size was small. This can possibly reflect oxidative stress in ICU patients. Further studies should reveal whether AGE-accumulation will be a useful parameter in ICU patients and whether skin AF has a predictive value for outcome, which was not shown in this small study.

  3. Accumulation of advanced glycation end (AGEs) products in intensive care patients: an observational, prospective study

    OpenAIRE

    Rommes Johannes H; Smit Jitty M; Greven Wendela L; Spronk Peter E

    2010-01-01

    Abstract Background Oxidative stress plays an important role in the course and eventual outcome in a majority of patients admitted to the intensive care unit (ICU). Markers to estimate oxidative stress are not readily available in a clinical setting. AGEs accumulation has been merely described in chronic conditions, but can also occur acutely due to oxidative stress. Since AGEs have emerged to be stable end products, these can be a marker of oxidative stress. Skin autofluorescence (AF) is a v...

  4. Accumulation of advanced glycation end products decreases collagen turnover by bovine chondrocytes

    NARCIS (Netherlands)

    Groot, J. de; Verzijl, N.; Budde, M.; Bijlsma, J.W.J.; Lafeber, F.P.J.G.; TeKoppele, J.M.

    2001-01-01

    The integrity of the collagen network is essential for articular cartilage to fulfill its function in load support and distribution. Damage to the collagen network is one of the first characteristics of osteoarthritis. Since extensive collagen damage is considered irreversible, it is crucial that ch

  5. Short-term effects of dietary advanced glycation end products in rats

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Andersen, Jeanette Marker; Hedegaard, Rikke Susanne Vingborg;

    2016-01-01

    excretion of N ε -carboxymethyl-lysine increased with increasing proportion of heat-treated milk powder in the HMW and LMW diets but was unrelated to gene expression. There was no difference in insulin sensitivity, F2-isoprostaglandins, food intake, water intake, body weight or body composition between......) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague-Dawley rats were fed a diet containing 20 % milk powder with different proportions of this being...

  6. Does hepatitis C increase the accumulation of advanced glycation end products in haemodialysis patients?

    NARCIS (Netherlands)

    Arsov, Stefan; Graaff, Reindert; Morariu, Aurora M.; van Oeveren, Wim; Smit, Andries J.; Busletic, Irena; Trajcevska, Lada; Selim, Gjulsen; Dzekova, Pavlina; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard

    2010-01-01

    Methods. AGE accumulation was measured by means of skin autofluorescence (AF) in 92 haemodialysis (HD) patients and 93 age-matched healthy controls. In the HD patients, CVD-related biochemical variables were also measured. The HD patients were tested for hepatitis C virus (HCV) antibodies and alloca

  7. The protective effects of pomelo extract (Citrus grandis L. Osbeck) against fructose-mediated protein oxidation and glycation

    OpenAIRE

    Caengprasath, Natarin; Ngamukote, Sathaporn; Mäkynen, Kittana; Adisakwattana, Sirichai

    2013-01-01

    Chronic hyperglycemia induces non-enzymatic protein glycation, which plays an important role in the development of diabetic complications. Immense efforts have been made to determine effective antiglycation compounds from natural products. Pomelo has shown beneficial effects for human health. The objective of this study was to determine the antiglycation effect of pomelo extract against fructose-mediated protein oxidation and glycation. Our results showed that the pomelo extract (0.25 - 2.00 ...

  8. Glycated Hemoglobin and Cancer Incidence and Mortality in the Atherosclerosis in Communities (ARIC) Study, 1990–2006

    OpenAIRE

    Joshu, Corinne E.; Prizment, Anna E.; Dluzniewski, Paul J.; Menke, Andy; Folsom, Aaron R.; Coresh, Josef; Yeh, Hsin C; Brancati, Frederick L.; Platz, Elizabeth A.; Selvin, Elizabeth

    2012-01-01

    Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in non-diabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood sa...

  9. Monitoring protein glycation by electrospray ionization (ESI) quadrupole time-of-flight (Q-TOF) mass spectrometer.

    Science.gov (United States)

    Akıllıoğlu, H Gül; Çelikbıçak, Ömür; Salih, Bekir; Gökmen, Vural

    2017-02-15

    In this study electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) mass spectrometry was used to investigate protein glycation. The glycated species of cytochrome C, lysozyme, and β-casein formed during glycation with d-glucose were identified and monitored in binary systems heated at 70°C under dry and aqueous conditions. Cytochrome C had multiple charges in non-glycated state, primarily changing from +13 to +17 positive charges, whereas β-casein had charge states up to +30. Upon heating with glucose at 70°C in aqueous state, attachment of one glucose molecule onto proteins was observed in each charge state. However, heating in dry state caused much more glucose attachment, leading to the formation of multiple glycoforms of proteins. By using ESI-QTOF-MS technique, formation of glycated cytochrome C containing up to 12 glucose moieties were observed, while glycated species containing 6 and 8 glucose moieties were observed for lysozyme and β-casein, respectively in various heating conditions. PMID:27664609

  10. Increased glycated Cu,Zn-superoxide dismutase levels in erythrocytes of patients with insulin-dependent diabetis mellitus.

    Science.gov (United States)

    Kawamura, N; Ookawara, T; Suzuki, K; Konishi, K; Mino, M; Taniguchi, N

    1992-06-01

    Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess glycated Cu,Zn-SOD in patients with insulin-dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus.

  11. Evaluation of Solvita compost stability and maturity tests for assessment of quality of end-products from mixed latrine style compost toilets

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Geoffrey B., E-mail: geoff.hill@geog.ubc.ca [University of British Columbia, Department of Geography, 1984 West Mall, Vancouver, Canada V6T 1Z2 (Canada); Baldwin, Susan A. [Chemical and Biological Engineering, University of British Columbia, 2360 East Mall, Vancouver, B.C., Canada V6T 1Z3 (Canada); Vinnerås, Bjorn [Swedish University of Agricultural Sciences, Box 7032, SE-750 07 Uppsala (Sweden)

    2013-07-15

    Highlights: • Solvita® stability and maturity tests used on composting toilet end-product. • Solvita® ammonia better suited in evaluation of feedstock suitability for vermicomposting. • No clear value of Solvita® stability test due to prevalent inhibition of decomposition by ammonia. - Abstract: It is challenging and expensive to monitor and test decentralized composting toilet systems, yet critical to prevent the mismanagement of potentially harmful and pathogenic end-product. Recent studies indicate that mixed latrine composting toilets can be inhibited by high ammonia content, a product of urea hydrolysis. Urine-diverting vermicomposting toilets are better able to accomplish the goals of remote site human waste management by facilitating the consumption of fecal matter by earthworms, which are highly sensitive to ammonia. The reliability of Solvita® compost stability and maturity tests were evaluated as a means of determining feedstock suitability for vermicomposting (ammonia) and end-product stability/completeness (carbon dioxide). A significant linear regression between Solvita® ammonia and free ammonia gas was found. Solvita® ranking of maturity did not correspond to ranking assigned by ammonium:nitrate standards. Solvita® ammonia values 4 and 5 contained ammonia levels below earthworm toxicity limits in 80% and 100% of samples respectively indicative of their use in evaluating feedstock suitability for vermicomposting. Solvita® stability tests did not correlate with carbon dioxide evolution tests nor ranking of stability by the same test, presumably due to in situ inhibition of decomposition and microbial respiration by ammonia which were reported by the Solvita® CO{sub 2} test as having high stability values.

  12. Evaluation of Solvita compost stability and maturity tests for assessment of quality of end-products from mixed latrine style compost toilets

    International Nuclear Information System (INIS)

    Highlights: • Solvita® stability and maturity tests used on composting toilet end-product. • Solvita® ammonia better suited in evaluation of feedstock suitability for vermicomposting. • No clear value of Solvita® stability test due to prevalent inhibition of decomposition by ammonia. - Abstract: It is challenging and expensive to monitor and test decentralized composting toilet systems, yet critical to prevent the mismanagement of potentially harmful and pathogenic end-product. Recent studies indicate that mixed latrine composting toilets can be inhibited by high ammonia content, a product of urea hydrolysis. Urine-diverting vermicomposting toilets are better able to accomplish the goals of remote site human waste management by facilitating the consumption of fecal matter by earthworms, which are highly sensitive to ammonia. The reliability of Solvita® compost stability and maturity tests were evaluated as a means of determining feedstock suitability for vermicomposting (ammonia) and end-product stability/completeness (carbon dioxide). A significant linear regression between Solvita® ammonia and free ammonia gas was found. Solvita® ranking of maturity did not correspond to ranking assigned by ammonium:nitrate standards. Solvita® ammonia values 4 and 5 contained ammonia levels below earthworm toxicity limits in 80% and 100% of samples respectively indicative of their use in evaluating feedstock suitability for vermicomposting. Solvita® stability tests did not correlate with carbon dioxide evolution tests nor ranking of stability by the same test, presumably due to in situ inhibition of decomposition and microbial respiration by ammonia which were reported by the Solvita® CO2 test as having high stability values

  13. Frequency of Mealtime Insulin Bolus Predicts Glycated Hemoglobin in Youths with Type 1 Diabetes

    OpenAIRE

    Patton, Susana R.; DeLurgio, Stephen A.; Fridlington, Amanda; Cohoon, Cyndy; Turpin, Angela L.; Clements, Mark A.

    2014-01-01

    Background: Within pediatric diabetes management, two electronic measures of adherence exist: frequency of daily blood glucose monitoring (BGM) and the BOLUS score, a measure of frequency of mealtime insulin bolusing. Past research has demonstrated that the BOLUS score is superior to daily BGM in predicting youths' glycated hemoglobin (HbA1c) in a cross-sectional study. We present data comparing the two adherence measures in predicting HbA1c using a prospective, longitudinal design.

  14. Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Valter; Donadon; Massimiliano; Balbi; Francesca; Valent; Angelo; Avogaro

    2010-01-01

    AIM: To evaluate the relationship between glycemic control [assessed by glycated hemoglobin (HbA1c)], antidiabetic therapies and the risk of hepatocellular carcinoma (HCC).METHODS: We recruited 465 patients with HCC, 618 cases with liver cirrhosis and 490 controls with no liver disease. Among subjects with type 2 diabetes mellitus (DM2), the associations between the antidiabetic strategies and HbA1c level with HCC were determined through 2 series of multivariate logistic regression models using cirrhotic pa...

  15. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

    OpenAIRE

    Xiaosong Li; Min Min; Nan Du; Ying Gu; Tomas Hode; Mark Naylor; Dianjun Chen; Nordquist, Robert E.; Chen, Wei R.

    2013-01-01

    With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development.

  16. Self Reported Halitosis in Relation to Glycated Hemoglobin Level in Diabetic Patients

    OpenAIRE

    Al-Zahrani, Mohammad S.; Zawawi, Khalid H; Austah, Obadah N; Al-Ghamdi, Hamed S

    2011-01-01

    Objective: This study was conducted to examine the relationship between the glycated hemoglobin level (HbA1c) and halitosis status among diabetic patients affected with periodontitis and to examine if there is a relationship between halitosis and different periodontal parameters. Methods and Materials: Consecutive type 2 diabetic patients were recruited from patients presented for treatment at a University hospital. Age, gender and smoking were recorded. A structured questionnaire on patients...

  17. Independent association between glycated hemoglobin and arterial stiffness in healthy men

    OpenAIRE

    Noh, Jin‐Won; Kim, Eun‐Jung; Seo, Hyun‐Ju; Kim, Soo Geun

    2015-01-01

    Abstract Aims/Introduction Many studies have reported that high levels of glycated hemoglobin (HbA1c) are strongly associated with an increased risk of cardiovascular disease. Many researchers have not studied the association of HbA1c with various subclinical atherosclerosis phenotypes. We evaluated the impact of HbA1c on arterial stiffness and atherosclerosis in healthy Korean healthy men. Materials and Methods The study population included healthy adult men who participated in health check‐...

  18. Potent SIRT1 enzyme-stimulating and anti-glycation activities of polymethoxyflavonoids from Kaempferia parviflora.

    Science.gov (United States)

    Nakata, Asami; Koike, Yuka; Matsui, Hirofumi; Shimadad, Tsutomu; Aburada, Masaki; Yang, Jinwei

    2014-09-01

    The SIRT1 enzyme-stimulating and anti-glycation activities of Kaempferia parviflora extract and its main polymethoxyflavonoids were evaluated in vitro. K. parviflora extract elevated SIRT1 catalytic activity by eight- and 17-fold at 20 μg/mL and 100 μg/mL, respectively, compared with vehicle only. Two major polymethoxyflavonoids, 3,5,7,3',4'-pentamethoxyflavone (4) and 5,7,4'-trimethoxyflavone (5), were isolated from this extract and are four- and fivefold more potent than resveratrol, hitherto the strongest known natural SIRT1 activator. In addition, the anti-glycation activity of K. parviflora extract was observed to be seven times more effective than aminoguanidine, a clinical anti-diabetes drug. 3,5,7,3',4'-Pentamethoxyflavone (4) and 5,7,4'-trimethoxyflavone (5) showed the strongest anti-glycation activity among the tested polymethoxyflavonoids. Further comparison of the activity of these structurally related polymethoxyflavonoids revealed a possible structure-activity relationship, in particular, for the contribution of methoxy moieties. PMID:25918795

  19. Correlation of Lipid Peroxidation with Glycated Haemoglobin Levels in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Varashree BS

    2011-07-01

    Full Text Available Reactive oxygen species are crucial to normal biological processes; they are potentially dangerous and are commonly referred to as prooxidants. The reactive oxygen intermediates can cause direct cellular injury by including lipid and protein peroxidation and damage to nucleic acid. The polyunsaturated fatty acids present in the cells are vulnerable to free radicals causing lipid peroxidation. Determination of Malondialdehyde (MDA by using thiobarbituric acid is used as an index of the extent of lipid peroxidation. This study was done to know if lipid peroxidation correlated with the glycated haemoglobin levels. Diabetic status was assessed by estimating fasting blood sugar and glycated haemoglobin level while oxidant stress was evaluated by estimating erythrocyte MDA levels. The lipid peroxidation in erythrocyte lysates was significantly increased in diabetic individuals compared to controls (p<0.001. The result of this study indicates that in diabetic individuals are more prone to oxidative stress and glycated haemoglobin is a marker in evaluating the long term glycemic status in diabetic individuals.

  20. 苦瓜提取物抑制蛋白质的非酶糖基化%Inhibitive Effects of Bitter Melon Extract on the Protein Non-enzymatic Glycation

    Institute of Scientific and Technical Information of China (English)

    陈绍红; 刘少彬; 赵云涛

    2012-01-01

    Objective; Using in vitro and in vivo models, the role of bitter melon extract on protein non-enzymatic glycation were investigated. Method; In vitro model, different doses of the extract (0. 01 , 0. 1 , 1. 0 g · L-1) or aminogunidine (4 mmol · L-l) were added, non-enzymatic glycation end products were measured at different time points by fluorescent measurer. In vivo model, diabetes mice were fed with different doses of extract (10, 30 g · kg-1) . The effects of bitter melon extract on blood glucose, advanced glycation end products ( AGEs) levels, superoxide dismutases (SOD) activity and maleic dialdehyde (MDA) content in heart, liver and kidney tissue were assayed. Result; In vitro system, protein glycation products formation was positively correlated with the incubation time, bitter melon extract inhibited the formation of advanced glycation end products dose-dependently (P < 0. 01) . Animal experiments showed that bitter melon extract inhibited blood sugar of diabetic mice (P < 0. 05 , P <0. 01). AGE levels and MDA content of heart, liver and kidney tissue were lowed significantly in group which fed with extract (P <0. 05, P <0. 01). Also, SOD activity was enhanced in group which fed with extract (P < 0. 05, P < 0. 01). Conclusion; Bitter melon extract have inhibitive effects on the formation of advanced glycation end products in vitro and in vivo.%目的:研究苦瓜提取物对蛋白质非酶糖基化终末产物( AGE)生成的抑制作用.方法:体外蛋白质非酶糖基化反应系统中分别加入不同质量浓度的苦瓜提取物(0.01,0.1,1.0 g·L-1)或氮基胍(4 mmol·L-1),在不同时间分别测定蛋白质非酶糖化终末产物的生成量.制备糖尿病小鼠模型,以苦瓜提取物10,30 g·kg-1两个剂量连续ig 14 d,测定苦瓜提取物对糖尿病小鼠血糖以及心、肝、肾组织中AGE含量、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量的影响.结果:在体外系统中,蛋白糖化产物的生成与孵育时间

  1. Possibilities for recycling cellulases after use in cotton processing: part I: Effects of end-product inhibition, thermal and mechanical deactivation, and cellulase depletion by adsorption.

    Science.gov (United States)

    Azevedo, Helena; Bishop, David; Cavaco-Paul, Artur

    2002-04-01

    Preliminary recycling experiments with cellulase enzymes after cotton treatments at 50 degrees C showed that activity remaining in the treatment liquors was reduced by about 80% after five recycling steps. The potential problems of end-product inhibition, thermal and mechanical deactivation, and the loss of some components of the cellulase complex by preferential and or irreversible adsorption to cotton substrates were studied. End-product inhibition studies showed that the build-up of cellobiose and glucose would be expected to cause no more than 40% activity loss after five textile treatment cycles. Thermal and mechanical treatments of cellulases suggested that the enzymes start to be deactivated at 60 degrees C and agitation levels similar to those used in textile processing did not cause significant enzyme deactivation. Analysis of cellulase solutions, by fast protein liquid chromatography, before and after adsorption on cotton fabrics, suggested that the cellobiohydrolase II (Cel6A) content of the cellulase complex was reduced, relative to the other components, by preferential adsorption. This would lead to a marked reduction in activity after several treatment cycles and top-up with pure cellobiohydrolase II would be necessary unless this component is easily recoverable from the treated fabric.

  2. Impact of Cyanidin-3-Glucoside on Glycated LDL-Induced NADPH Oxidase Activation, Mitochondrial Dysfunction and Cell Viability in Cultured Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xueping Xie

    2012-11-01

    Full Text Available Elevated levels of glycated low density lipoprotein (glyLDL are frequently detected in diabetic patients. Previous studies demonstrated that glyLDL increased the production of reactive oxygen species (ROS, activated NADPH oxidase (NOX and suppressed mitochondrial electron transport chain (mETC enzyme activities in vascular endothelial cells (EC. The present study examined the effects of cyanidin-3-glucoside (C3G, a type of anthocyanin abundant in dark-skinned berries, on glyLDL-induced ROS production, NOX activation and mETC enzyme activity in porcine aortic EC (PAEC. Co-treatment of C3G prevented glyLDL-induced upregulation of NOX4 and intracellular superoxide production in EC. C3G normalized glyLDL-induced inhibition on the enzyme activities of mETC Complex I and III, as well as the abundances of NADH dehydrogenase 1 in Complex I and cytochrome b in Complex III in EC. Blocking antibody for the receptor of advanced glycation end products (RAGE prevented glyLDL-induced changes in NOX and mETC enzymes. Combination of C3G and RAGE antibody did not significantly enhance glyLDL-induced inhibition of NOX or mETC enzymes. C3G reduced glyLDL-induced RAGE expression with the presence of RAGE antibody. C3G prevented prolonged incubation with the glyLDL-induced decrease in cell viability and the imbalance between key regulators for cell viability (cleaved caspase 3 and B cell Lyphoma-2 in EC. The findings suggest that RAGE plays an important role in glyLDL-induced oxidative stress in vascular EC. C3G may prevent glyLDL-induced NOX activation, the impairment of mETC enzymes and cell viability in cultured vascular EC.

  3. Product and process understanding to relate the effect of freezing method on glycation and aggregation of lyophilized monoclonal antibody formulations.

    Science.gov (United States)

    Awotwe-Otoo, David; Agarabi, Cyrus; Read, Erik K; Lute, Scott; Brorson, Kurt A; Khan, Mansoor A

    2015-07-25

    The objective of the study was to analyze the effect of controlled and uncontrolled freezing step of a lyophilization process on the extent of non-enzymatic glycation and aggregation of an IgG1 formulation at two concentrations (1mg/ml and 20mg/ml). The degree of glycation (%) was determined through boronate affinity chromatography and its effect on the formation of soluble aggregates and higher molecular weight species was studied using dynamic light scattering (DLS) and size exclusion chromatography with multi-angle light scattering (SEC-MALS). The effect of non-enzymatic glycation on the secondary structure of the formulations was also studied using circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. Results indicated that controlled nucleation yielded higher residual moisture contents and significantly lower specific surface areas for the two monoclonal antibody concentrations compared with uncontrolled nucleation cycle (p<0.05). For the two concentrations, uncontrolled nucleation resulted in significantly higher levels of glycation compared with controlled nucleation samples (p<0.05). Further, it was observed that higher storage temperatures (25°C/60% RH) versus 5°C resulted in higher glycation. Even though SEC-MALS analyses of the low concentrated formulations did not reveal the formation of higher molecular weight species, DLS analyses at two storage conditions revealed increases in the hydrodynamic radii and polydispersity index of the reconstituted formulations, suggesting the onset of formation of smaller species in the formulations. CD spectroscopy did not reveal any differences in the secondary structure of the mAb for the two concentrations after lyophilization. In conclusion, the freezing step method impacted the extent of glycation in lyophilized samples and the hydrolyzed component of sucrose was critical for increasing glycation. Even though some level of glycation was observed in lyophilized samples, the

  4. Advanced Purex process for the new French reprocessing plants

    International Nuclear Information System (INIS)

    The paper describes the main process innovations of the new Cogema reprocessing plants of La Hague (UP3 and UP2 800). Major improvements of process like the use of rotary dissolvers and annular columns, and also entirely new processes like solvent distillation and plutonium oxidizing dissolution, yield an advanced Purex process. The results of these innovations are significant improvements for throughput, end-products purification performances and waste minimization. They contribute also to limit personnel exposure. The main results of the first three years of operation are described. (author). 3 refs., 5 figs

  5. Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Farlay, Delphine; Armas, Laura A G; Gineyts, Evelyne; Akhter, Mohammed P; Recker, Robert R; Boivin, Georges

    2016-01-01

    Low-energy fractures are frequent complications in type 1 diabetes mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced glycation end products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and nonfracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and nonfracturing T1DM versus CTL. We analyzed iliac crest bone biopsies from 5 fracturing T1DM patients, 5 nonfracturing T1DM patients, and 5 healthy subjects, all age- and sex-matched. AGEs (pentosidine) in bone matrix was measured by high-performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Trabecular bone from fracturing T1DM exhibited significantly higher levels of pentosidine than CTL (p = 0.04) and was more mineralized than nonfracturing T1DM (p = 0.04) and CTL (p = 0.04). Trabecular bone was not significantly different in pentosidine between nonfracturing T1DM and CTL. Cortical bone from nonfracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and pentosidine (r' = 0.79, p < 0.003) and between HbA1c and DMB (r' = 0.64, p < 0.02). Both modifications could lead to less flexible bone (reduced modulus of elasticity) and a tendency toward low-energy fractures in T1DM patients.

  6. Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study: results from the Kyushu and Okinawa Populaiton Study (KOPS)

    Science.gov (United States)

    Glycated albumin is a measure of the mean plasma glucose concentration over approximately 2-3 weeks. We determined reference values for glycated albumin, and assessed its utility for the diagnosis of type 2 diabetes mellitus in the general population. We studied 1,575 men and women (mean age, 49.9 y...

  7. Quantification of glycated N-terminal peptide of hemoglobin using derivatization for multiple functional groups of amino acids followed by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Sakaguchi, Yohei; Kinumi, Tomoya; Yamazaki, Taichi; Takatsu, Akiko

    2016-02-01

    A novel method of amino acid analysis using derivatization of multiple functional groups (amino, carboxyl, and phenolic hydroxyl groups) was applied to measure glycated amino acids in order to quantify glycated peptides and evaluate the degree of glycation of peptide. Amino and carboxyl groups of amino acids were derivatized with 1-bromobutane so that the hydrophobicities and basicities of the amino acids, including glycated amino acids, were improved. These derivatized amino acids could be detected with high sensitivity using LC-MS/MS. In this study, 1-deoxyfructosyl-VHLTPE and VHLTPE, which are N-terminal peptides of the β-chains of hemoglobin, were selected as target compounds. After reducing the peptide sample solution with sodium borohydride, the obtained peptides were hydrolyzed with hydrochloric acid. The released amino acids were then derivatized with 1-bromobutane and analyzed with LC-MS/MS. The derivatized amino acids, including glycated amino acids, could be separated using an octadecyl silylated silica column and good sharp peaks were detected. We show a confirmatory experiment that the proposed method can be applied to evaluate the degree of glycation of peptides, using mixtures of glycated and non-glycated peptide.

  8. Oxidative Damage to DNA and Lipids: Correlation with Protein Glycation in Patients with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    M.T. Goodarzi

    2008-01-01

    Full Text Available Introduction & Objective: Diabetic hyperglycemia is associated with increased production of Reactive Oxygen Species (ROS. ROS reacts with DNA results in products such as 8-hydroxydeoxyguanosine that excrete in urine due to DNA repair processes. This study aims to evaluate correlation between oxidative damage of DNA and protein glycation in patients with Type 1 diabetes. We measured urinary 8-OHdG level in diabetic and control group and evaluated its correlation to glycated hemoglobin (HbA1c and glycated serum protein (GSP levels. Furthermore plasma malondialdehyde (MDA level was measured as an important indicator of lipid peroxidation in diabetes.Materials & Methods: We studied 32 patients with diabetes mellitus Type 1 and compared them with 48 sex and age-matched non-diabetic controls. GSP and MDA measurement were made by colorimetric assay. Hemoglobin A1c measured by ion-exchange chromatography method and urinary 8-OHdG measurement was made by competitive in vitro enzyme-linked immunosorbent assay (ELISA.Results: In the present study urinary 8-OHdG, blood HbA1c, plasma MDA and GSP levels were significantly higher in diabetics comparing to the control subjects (P<0.05. Furthermore, we found significant correlation between urinary 8-OHdG and HbA1c (P<0.05 in diabetic group. In addition, fasting blood sugar showed significant correlation with GSP and MDA (P<0.05. However the correlation of MDA with HbA1c was not significant in diabetic patients.Conclusion: This case-control study in young diabetic patients showed that increased blood glucose and related metabolic disorders result in oxidative stress and oxidative damage to DNA and lipids. Furthermore oxidative damage to DNA correlated to glycemic control, while there was no significant correlation between lipid peroxidation and the level of HbA1c.

  9. Glycated Hemoglobin and Incident Type 2 Diabetes in Singaporean Chinese Adults: The Singapore Chinese Health Study

    OpenAIRE

    Bancks, Michael P.; Odegaard, Andrew O.; Woon-Puay Koh; Jian-Min Yuan; Gross, Myron D.; Mark A. Pereira

    2015-01-01

    Background The American Diabetes Association recently included glycated hemoglobin in the diagnostic criteria for diabetes, but research on the utility of this biomarker in Southeast Asians is scant. The aim of this study was to evaluate the association between percent HbA1c and incident diabetes in an Asian population of adult men and women without reported diabetes. Methods Data analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study who provided a blood sample at the...

  10. Skin beautification with oral non-hydrolized versions of carnosine and carcinine: Effective therapeutic management and cosmetic skincare solutions against oxidative glycation and free-radical production as a causal mechanism of diabetic complications and skin aging.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Savel'yeva, Ekaterina L; Lankin, Vadim Z; Yegorov, Yegor E

    2012-10-01

    Advanced glycation Maillard reaction end products (AGEs) are causing the complications of diabetes and skin aging, primarily via adventitious and cross-linking of proteins. Long-lived proteins such as structural collagen are particularly implicated as pathogenic targets of AGE processes. The formation of α-dicarbonyl compounds represents an important step for cross-linking proteins in the glycation or Maillard reaction. The purpose of this study was to investigate the contribution of glycation coupled to the glycation free-radical oxidation reactions as markers of protein damage in the aging of skin tissue proteins and diabetes. To elucidate the mechanism for the cross-linking reaction, we studied the reaction between a three-carbon α-dicarbonyl compound, methy