Displaying publications 21 - 40 of 84 in total

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  1. An unbiased approach for analysis of protein glycosylation and application to influenza vaccine hemagglutinin
    An Y, Cipollo JF
    Anal Biochem, 2011 Aug 1;415(1):67-80.
    PMID: 21545787 DOI: 10.1016/j.ab.2011.04.018
    Here a mass spectrometry-based platform for the analysis of glycoproteins is presented. Glycopeptides and released glycans are analyzed, the former by quadrupole orthogonal time-of-flight liquid chromatography/mass spectrometry (QoTOF LC/MS) and the latter by permethylation analysis using matrix-assisted laser desorption/ionization (MALDI)-TOF MS. QoTOF LC/MS analysis reveals the stochastic distribution of glycoforms at occupied sequons, and the latter provides a semiquantitative assessment of overall protein glycosylation. Hydrophilic interaction chromatography (HILIC) was used for unbiased enrichment of glycopeptides and was validated using five model N-glycoproteins bearing a wide array of glycans, including high-mannose, complex, and hybrid subtypes such as sulfo and sialyl forms. Sialyl and especially sulfated glycans are difficult to analyze because these substitutions are labile. The conditions used here allow detection of these compounds quantitatively, intact, and in the context of overall glycosylation. As a test case, we analyzed influenza B/Malaysia/2506/2004 hemagglutinin, a component of the 2006-2007 influenza vaccine. It bears 11 glycosylation sites. Approximately 90% of its glycans are high mannose, and 10% are present as complex and hybrid types, including those with sulfate. The stochastic distribution of glycoforms at glycosylation sites is revealed. This platform should have wide applications to glycoproteins in basic sciences and industry because no apparent bias for any glycoforms is observed.
    Matched MeSH terms: Glycosylation*
  2. Fulltext The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk
    Kong SY, Takeuchi M, Hyogo H, McKeown-Eyssen G, Yamagishi S, Chayama K, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Dec;24(12):1855-63.
    PMID: 26404963 DOI: 10.1158/1055-9965.EPI-15-0422
    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 from sugars such as glyceraldehyde. Glyceraldehyde contributes to the production of a group of compounds known as glyceraldehyde-derived advanced glycation end-products (glycer-AGEs), which may promote colorectal cancer through their proinflammatory and pro-oxidative properties. The objective of this study nested within a prospective cohort was to explore the association of circulating glycer-AGEs with risk of colorectal cancer.

    METHODS: A total of 1,055 colorectal cancer cases (colon n = 659; rectal n = 396) were matchced (1:1) to control subjects. Circulating glycer-AGEs were measured by a competitive ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (95% CI), adjusting for potential confounding factors, including smoking, alcohol, physical activity, body mass index, and diabetes status.

    RESULTS: Elevated glycer-AGEs levels were not associated with colorectal cancer risk (highest vs. lowest quartile, 1.10; 95% CI, 0.82-1.49). Subgroup analyses showed possible divergence by anatomical subsites (OR for colon cancer, 0.83; 95% CI, 0.57-1.22; OR for rectal cancer, 1.90; 95% CI, 1.14-3.19; Pheterogeneity = 0.14).

    CONCLUSIONS: In this prospective study, circulating glycer-AGEs were not associated with risk of colon cancer, but showed a positive association with the risk of rectal cancer.

    IMPACT: Further research is needed to clarify the role of toxic products of carbohydrate metabolism and energy excess in colorectal cancer development.

    Matched MeSH terms: Glycosylation End Products, Advanced/blood*
  3. Fulltext Advanced glycation end products-related modulation of cathepsin L and NF-κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα
    Sharif U, Mahmud NM, Kay P, Yang YC, Harding SP, Grierson I, et al.
    J Cell Mol Med, 2019 01;23(1):405-416.
    PMID: 30338926 DOI: 10.1111/jcmm.13944
    The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age-related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)-known to accumulate on the ageing RPE's underlying Bruch's membrane in situ-on both key lysosomal cathepsins and NF-κB signalling in RPE. Cathepsin L activity and NF-κB effector levels decreased significantly following 2-week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE-related change of NF-κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE-exposed cells had significantly higher ratio of phospho-p65(Ser536)/total p65 compared to non-AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE-related activation of NF-κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF-κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para-inflammatory) mechanism but renders them more responsive to pro-inflammatory stimuli.
    Matched MeSH terms: Glycosylation End Products, Advanced/metabolism*
  4. Fulltext Impact of HMGB1, RAGE, and TLR4 in Alzheimer's Disease (AD): From Risk Factors to Therapeutic Targeting
    Paudel YN, Angelopoulou E, Piperi C, Othman I, Aamir K, Shaikh MF
    Cells, 2020 02 07;9(2).
    PMID: 32046119 DOI: 10.3390/cells9020383
    Alzheimer's disease (AD) is a devastating neurodegenerative disorder and a leading cause of dementia, with accumulation of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) as defining pathological features. AD presents a serious global health concern with no cure to date, reflecting the complexity of its pathogenesis. Recent evidence indicates that neuroinflammation serves as the link between amyloid deposition, Tau pathology, and neurodegeneration. The high mobility group box 1 (HMGB1) protein, an initiator and activator of neuroinflammatory responses, has been involved in the pathogenesis of neurodegenerative diseases, including AD. HMGB1 is a typical damage-associated molecular pattern (DAMP) protein that exerts its biological activity mainly through binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). RAGE and TLR4 are key components of the innate immune system that both bind to HMGB1. Targeting of HMGB1, RAGE, and TLR4 in experimental AD models has demonstrated beneficial effects in halting AD progression by suppressing neuroinflammation, reducing Aβ load and production, improving spatial learning, and inhibiting microglial stimulation. Herein, we discuss the contribution of HMGB1 and its receptor signaling in neuroinflammation and AD pathogenesis, providing evidence of its beneficial effects upon therapeutic targeting.
    Matched MeSH terms: Advanced Glycosylation End Product-Specific Receptor/metabolism*
  5. Unraveling the Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Myasthenia Gravis
    Angelopoulou E, Paudel YN, Piperi C
    ACS Chem Neurosci, 2020 03 04;11(5):663-673.
    PMID: 32017530 DOI: 10.1021/acschemneuro.9b00678
    Myasthenia gravis (MG) is an autoimmune T cell-dependent B cell-mediated disorder of the neuromuscular junction (NMJ) characterized by fluctuating skeletal muscle weakness, most commonly attributed to pathogenic autoantibodies against postsynaptic nicotinic acetylcholine receptors (AChRs). Although MG pathogenesis is well-documented, there are no objective biomarkers that could effectively correlate with disease severity or MG clinical subtypes, and current treatment approaches are often ineffective. The receptor for advanced glycation end products (RAGE) is a multiligand cell-bound receptor highly implicated in proinflammatory responses and autoimmunity. Preclinical evidence demonstrates that RAGE and its ligand S100B are upregulated in rat models of experimental autoimmune myasthenia gravis (EAMG). S100B-mediated RAGE activation has been shown to exacerbate EAMG, by enhancing T cell proinflammatory responses, aggravating T helper (Th) subset imbalance, increasing AChR-specific T cell proliferative capacity, and promoting the production of antibodies against AChRs from the spleen. Soluble sRAGE and esRAGE, acting as decoys of RAGE ligands, are found to be significantly reduced in MG patients. Moreover, MG has been associated with increased serum levels of S100A12, S100B and HMGB1. Several studies have shown that the presence of thymic abnormalities, the onset age of MG, and the duration of the disease may affect the levels of these proteins in MG patients. Herein, we discuss the emerging role of RAGE and its ligands in MG immunopathogenesis, their clinical significance as promising biomarkers, as well as the potential therapeutic implications of targeting RAGE signaling in MG treatment.
    Matched MeSH terms: Advanced Glycosylation End Product-Specific Receptor; Glycosylation End Products, Advanced
  6. N-linked glycolipids by Staudinger coupling of glycosylated alkyl diazides with fatty acids
    Salman SM, Heidelberg T, Bin Tajuddin HA
    Carbohydr Res, 2013 Jun 28;375:55-62.
    PMID: 23685811 DOI: 10.1016/j.carres.2013.03.028
    Aiming for new glycolipids with enhanced chemical stability and close structural similarity to natural cell membrane lipids for the development of a drug delivery system, we have synthesized double amide analogs of glyco-glycerolipids. The synthesis applied a Staudinger reaction based coupling of a 1,3-diazide with fatty acid chlorides. While the concept furnished the desired glucosides in reasonable yields, the corresponding lactosides formed a tetrahydropyrimidine based 1:1 coupling product instead. This unexpected coupling result likely originates from steric hindrance at the iminophosphorane intermediate and provides an interesting core structure for potentially bioactive surfactants. The assembly behavior of both glycolipid types was investigated by optical polarizing microscopy, DSC and surface tension studies.
    Matched MeSH terms: Glycosylation
  7. Fulltext Revealing Glycoproteins in the Secretome of MCF-7 Human Breast Cancer Cells
    Tan AA, Phang WM, Gopinath SC, Hashim OH, Kiew LV, Chen Y
    Biomed Res Int, 2015;2015:453289.
    PMID: 26167486 DOI: 10.1155/2015/453289
    Breast cancer is one of the major issues in the field of oncology, reported with a higher prevalence rate in women worldwide. In attempt to reveal the potential biomarkers for breast cancer, the findings of differentially glycosylated haptoglobin and osteonectin in previous study have drawn our attention towards glycoproteins of secretome from the MCF-7 cancer cell line. In the present study, further analyses were performed on the medium of MCF-7 cells by subjecting it to two-dimensional analyses followed by image analysis in contrast to the medium of human mammary epithelial cells (HMEpC) as a negative control. Carboxypeptidase A4 (CPA4), alpha-1-antitrypsin (AAT), haptoglobin (HP), and HSC70 were detected in the medium of MCF-7, while only CPA4 and osteonectin (ON) were detected in HMEpC medium. In addition, CPA4 was detected as upregulated in the MCF-7 medium. Further analysis by lectin showed that CPA4, AAT, HP, and HSC70 were secreted as N-glycan in the medium of MCF-7, with HP also showing differentially N-glycosylated isoforms. For the HMEpC, only CPA4 was detected as N-glycan. No O-glycan was detected in the medium of HMEpC but MCF-7 expressed O-glycosylated CPA4 and HSC70. All these revealed that glycoproteins could be used as glycan-based biomarkers for the prognosis of breast cancer.
    Matched MeSH terms: Glycosylation
  8. How glycosylation aids tumor angiogenesis: An updated review
    Cheng WK, Oon CE
    Biomed Pharmacother, 2018 Jul;103:1246-1252.
    PMID: 29864905 DOI: 10.1016/j.biopha.2018.04.119
    Glycosylation is an enzymatic process in which a carbohydrate is attached to a functional group from another molecule. Glycosylation is a crucial post translational process in protein modification. The tumor microenvironment produces altered glycans that contribute to cancer progression and aggressiveness. Abnormal glycosylation is widely observed in tumor angiogenesis. Despite many attempts to decipher the role of glycosylation in different aspects of cancer, little is known regarding the roles of glycans in angiogenesis. The blood vessels in tumors are often used to transport oxygen and nutrients for tumor progression and metastasis. The crosstalk within the tumor microenvironment can induce angiogenesis by manipulating these glycans to hijack the normal angiogenesis process, thus promoting tumor growth. Abnormal glycosylation has been shown to promote tumor angiogenesis by degrading the extracellular matrix to activate the angiogenic signaling pathways. This review highlights the latest update on how glycosylation can contribute to tumor angiogenesis that may affect treatment outcomes.
    Matched MeSH terms: Glycosylation
  9. Glycosylated biomarker sensors: advancements in prostate cancer diagnosis
    Abd Rahman SF, Md Arshad MK, Gopinath SCB, Fathil MFM, Sarry F, Ibau C
    Chem Commun (Camb), 2021 Sep 23;57(76):9640-9655.
    PMID: 34473143 DOI: 10.1039/d1cc03080a
    Prostate cancer is currently diagnosed using the conventional gold standard methods using prostate-specific antigen (PSA) as the selective biomarker. However, lack of precision in PSA screening has resulted in needless biopsies and delays the treatment of potentially fatal prostate cancer. Thus, identification of glycans as novel biomarkers for the early detection of prostate cancer has attracted considerable attention due to their reliable diagnostic platform compared with the current PSA systems. Therefore, biosensing technologies that provide point-of-care diagnostics have demonstrated the ability to detect various analytes, including glycosylated micro- and macro-molecules, thereby enabling versatile detection methodologies. This highlight article discusses recent advances in the biosensor-based detection of prostate cancer glycan biomarkers and the innovative strategies for the conjugation of nanomaterials adapted to biosensing platforms. Finally, the article is concluded with prospects and challenges of prostate cancer biosensors and recommendations to overcome the issues associated with prostate cancer diagnosis.
    Matched MeSH terms: Glycosylation
  10. The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition
    Khangholi S, Majid FA, Berwary NJ, Ahmad F, Aziz RB
    Planta Med, 2016 Jan;82(1-2):32-45.
    PMID: 26550791 DOI: 10.1055/s-0035-1558086
    Glycation, the non-enzymatic binding of glucose to free amino groups of an amino acid, yields irreversible heterogeneous compounds known as advanced glycation end products. Those products play a significant role in diabetic complications. In the present article we briefly discuss the contribution of advanced glycation end products to the pathogenesis of diabetic complications, such as atherosclerosis, diabetic retinopathy, nephropathy, neuropathy, and wound healing. Then we mention the various mechanisms by which polyphenols inhibit the formation of advanced glycation end products. Finally, recent supporting documents are presented to clarify the inhibitory effects of polyphenols on the formation of advanced glycation end products. Phytochemicals apply several antiglycation mechanisms, including glucose metabolism, amelioration of oxidative stress, scavenging of dicarbonyl species, and up/down-regulation of gene expression. To utilize polyphenols in order to remedy diabetic complications, we must explore, examine and clarify the action mechanisms of the components of polyphenols.
    Matched MeSH terms: Glycosylation
  11. Fulltext Lectins: an effective tool for screening of potential cancer biomarkers
    Hashim OH, Jayapalan JJ, Lee CS
    PeerJ, 2017;5:e3784.
    PMID: 28894650 DOI: 10.7717/peerj.3784
    In recent years, the use of lectins for screening of potential biomarkers has gained increased importance in cancer research, given the development in glycobiology that highlights altered structural changes of glycans in cancer associated processes. Lectins, having the properties of recognizing specific carbohydrate moieties of glycoconjugates, have become an effective tool for detection of new cancer biomarkers in complex bodily fluids and tissues. The specificity of lectins provides an added advantage of selecting peptides that are differently glycosylated and aberrantly expressed in cancer patients, many of which are not possibly detected using conventional methods because of their low abundance in bodily fluids. When coupled with mass spectrometry, research utilizing lectins, which are mainly from plants and fungi, has led to identification of numerous potential cancer biomarkers that may be used in the future. This article reviews lectin-based methods that are commonly adopted in cancer biomarker discovery research.
    Matched MeSH terms: Glycosylation
  12. Fulltext Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets
    Safi SZ, Qvist R, Kumar S, Batumalaie K, Ismail IS
    Biomed Res Int, 2014;2014:801269.
    PMID: 25105142 DOI: 10.1155/2014/801269
    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.
    Matched MeSH terms: Glycosylation End Products, Advanced/metabolism
  13. Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their biological activities
    Taha M, Ismail NH, Jamil W, Rashwan H, Kashif SM, Sain AA, et al.
    Eur J Med Chem, 2014 Sep 12;84:731-8.
    PMID: 25069019 DOI: 10.1016/j.ejmech.2014.07.078
    4-Methylbenzimidazole 1-28 novel derivatives were synthesized and evaluated for their antiglycation and antioxidant activities. Compounds 1-7 and 11 showed excellent activities ranged 140-280 μM, better than standard drug rutin (294.46 ± 1.50 μM). Compound 1-28 were also evaluated for DPPH activities. Compounds 1-8 showed excellent activities, ranging 12-29 μM, better than standard drug n-propylgallate (IC50 = 30.30 ± 0.40 μM). For superoxide anion scavenging activity, compounds 1-7 showed better activity than standard n-propylgallate (IC50 = 106.34 ± 1.6 μM), ranged 82-104 μM. These compounds were found to be nontoxic to THP-1 cells.
    Matched MeSH terms: Glycosylation/drug effects
  14. Fulltext Lack of association between Gly82Ser, 1704G/T and 2184A/G of RAGE gene polymorphisms and retinopathy susceptibility in Malaysian diabetic patients
    Ng ZX, Kuppusamy UR, Poh R, Tajunisah I, Koay AC, Fong KC, et al.
    Genet. Mol. Res., 2012 Mar 01;11(1):455-61.
    PMID: 22427038 DOI: 10.4238/2012.March.1.2
    Diabetic retinopathy is the most common diabetic eye disease, occurring in about 60% of type 2 diabetic patients. Other than known clinical risk factors, the influence of genes has been suggested as part of the development of diabetic retinopathy. We investigated the association of Gly82Ser, 1704G/T and 2184A/G polymorphisms in the RAGE gene with retinopathy in type 2 diabetic patients in Malaysia. Ninety-eight unrelated retinopathy patients and 185 unrelated healthy controls from all over Malaysia were recruited in this study. The allele and genotype frequencies of the three gene polymorphisms were investigated using PCR-RFLP. The allele frequency of the three polymorphisms did not differ significantly between the control and the retinopathy group (P > 0.05). Analysis of the frequency of GA+AA, GT+TT and AG+GG in the retinopathy group did not reveal significant differences (P > 0.05) compared to the control group. We conclude that RAGE gene Gly82Ser, 1704G/T and 2184A/G polymorphisms are not associated with retinopathy development in the Malaysian population.
    Matched MeSH terms: Advanced Glycosylation End Product-Specific Receptor/genetics*
  15. Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus
    Kuppusamy UR, Indran M, Ahmad T, Wong SW, Tan SY, Mahmood AA
    Clin Chim Acta, 2005 Jan;351(1-2):197-201.
    PMID: 15563890 DOI: 10.1016/j.cccn.2004.09.014
    BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population.
    METHOD: The assays were carried out according to known established protocols.
    RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels.
    CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.
    Matched MeSH terms: Glycosylation End Products, Advanced/blood
  16. Effect of Tai Chi exercise on DNA damage, antioxidant enzymes, and oxidative stress in middle-age adults
    Goon JA, Aini AH, Musalmah M, Anum MY, Nazaimoon WM, Ngah WZ
    J Phys Act Health, 2009 Jan;6(1):43-54.
    PMID: 19211957
    BACKGROUND: The biochemical mechanisms involving oxidative stress to explain the relationship between exercise and healthy aging are still unclear.

    METHODS: Tai Chi participants and matched sedentary volunteers age 45 and above were enrolled. Glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities; levels of DNA damage using the comet assay; and malondialdehyde (MDA) and advanced glycation end products (AGE) were determined at 0, 6, and 12 months.

    RESULTS: Tai Chi subjects had decreased normal and increased mildly damaged DNA with elevated GPx activity after 6 months (n=25). Plasma MDA and AGE concentrations decreased significantly after 12 months (n=15) accompanied by increased SOD activity. This may be attributed to the hormesis effect, whereby mild induction of oxidative stress at the first 6 months of exercise resulted in stimulation of antioxidant defenses. These parameters were unchanged in the sedentary subjects in the first 6 months (n=27) except for elevated SOD activity. After 12 months, the sedentary subjects (n=17) had decreased normal DNA and increased severely damaged DNA with unaltered MDA and AGE levels while SOD and GPx activities were significantly elevated.

    CONCLUSION: Regular Tai Chi exercise stimulated endogenous antioxidant enzymes and reduced oxidative damage markers.

    Matched MeSH terms: Glycosylation End Products, Advanced/blood
  17. Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and sRAGE in diabetic retinopathy
    Ng ZX, Kuppusamy UR, Iqbal T, Chua KH
    Gene, 2013 Jun 1;521(2):227-33.
    PMID: 23545311 DOI: 10.1016/j.gene.2013.03.062
    Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear.
    Matched MeSH terms: Advanced Glycosylation End Product-Specific Receptor; Glycosylation End Products, Advanced/metabolism
  18. Protective effect of different parts of Cassia fistula on human umbilical vein endothelial cells against glycated protein-induced toxicity in vitro
    Einstein JW, Mustafa MR, Nishigaki I, Rajkapoor B, Moh MA
    Methods Find Exp Clin Pharmacol, 2008 Oct;30(8):599-605.
    PMID: 19088944 DOI: 10.1358/mf.2008.30.8.1268401
    The protective effect of methanol extracts of Cassia fistula (flowers, leaves and bark) was examined in vitro in human umbilical vein endothelial cells (HUVEC) against toxicity induced by glycated protein (GFBS) in vitro. The experiments consisted of eight groups of HUVEC with five flasks in each group. Group I was treated with 15% FBS, group II with GFBS (70 microM) alone, and the other six groups were treated with GFBS plus 25 and 50 microg of each of the three types of C. fistula extracts. After 72 h of incubation, cells were collected and tested for lipid peroxidation, antioxidant enzyme activities and glutathione S-transferase (GST). The protective effect of C. fistula extracts against GFBS-induced cytotoxicity was examined in HUVEC by using trypan blue exclusion and MTT assays. Results showed that HUVEC incubated with GFBS alone showed a significant (P < 0.001) elevation of lipid peroxidation accompanied by depletion of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to decreased cytosolic GST. Treatment of HUVEC with C. fistula extracts at a concentration of 25 and 50 microg significantly decreased lipid peroxidation and normalized the activities of the antioxidant enzymes and GST levels in a concentration-dependent manner. Morphological changes of HUVEC were compared with respective controls; in addition, the C. fistula extracts increased the viability of HUVEC damaged by GFBS. A protective effect of C. fistula extracts on HUVEC against GFBS-induced toxicity suggested a potential beneficial effect of the extract in preventing diabetic angiopathies.
    Matched MeSH terms: Glycosylation; Glycosylation End Products, Advanced/metabolism
  19. New isatin derivative inhibits neurodegeneration by restoring insulin signaling in brain
    Aftab MF, Afridi SK, Mughal UR, Karim A, Haleem DJ, Kabir N, et al.
    J. Chem. Neuroanat., 2017 04;81:1-9.
    PMID: 28093241 DOI: 10.1016/j.jchemneu.2017.01.001
    Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration. Methylglyoxal induced stress was inhibited by treatment with URM-II-81. Also, Ser473 and Ser9 phosphorylation of Akt and GSK-3β respectively were restored by URM-II-81. Effect of URM-II-81 on axonal integrity was studied by differentiating Neuro2A using retinoic acid. URM-II-81 restored axonal length in MGO treated cells. Its effects were also studied in high fat and low dose streptozotocin induced diabetic mice where it reduced RBG levels and inhibited glycative stress by reducing HbA1c. URM-II-81 treatment also showed inhibition of gliosis in hippocampus. Histological analysis showed reduced NFTs in CA3 hippocampal region and restoration of insulin signaling in hippocampii of diabetic mice. Our findings suggest that URM-II-81 can be developed as a new therapeutic agent for treatment of neurodegenration.
    Matched MeSH terms: Glycosylation End Products, Advanced/antagonists & inhibitors; Glycosylation End Products, Advanced/metabolism
  20. Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients
    Nazratun N, Mahmood AA, Kuppusamy UR, Ahmad TS, Tan SY
    Vasc Med, 2006 Nov;11(4):245-50.
    PMID: 17390548
    The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.
    Matched MeSH terms: Glycosylation End Products, Advanced/metabolism*
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