38 results on '"Vanhooren V"'
Search Results
2. Abstract # 4268 Alterations of the serum N-glycan profile in female patients with Major Depressive Disorder
- Author
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Hitzler, M., primary, Boeck, C., additional, Pfister, S., additional, Buerkle, A., additional, Vanhooren, V., additional, Libert, C., additional, Salinas-Manrique, J., additional, Dietrich, D.E., additional, Kolassa, I.T., additional, and Karabatsiakis, A., additional
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- 2019
- Full Text
- View/download PDF
3. Determining differentially expressed miRNAs and validating miRNA—target relationships using the SPRET/Ei mouse strain
- Author
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Timmermans, S., primary, Van Hauwermeiren, F., additional, Puimège, L., additional, Dejager, L., additional, Van Wonterghem, E., additional, Vanhooren, V., additional, Mestdagh, P., additional, Libert, C., additional, and Vandenbroucke, R. E., additional
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- 2014
- Full Text
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4. N-glycosylation profiling of plasma provides evidence for accelerated physiological aging in post-traumatic stress disorder
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Moreno-Villanueva, M., Morath, J., Vanhooren, V., Elbert, T., Kolassa, S., Libert, C., Bürkle, A., Kolassa, I.-T., Moreno-Villanueva, M., Morath, J., Vanhooren, V., Elbert, T., Kolassa, S., Libert, C., Bürkle, A., and Kolassa, I.-T.
- Abstract
The prevalence of age-related diseases is increased in individuals with post-traumatic stress disorder (PTSD). However, the underlying biological mechanisms are still unclear. N-glycosylation is an age-dependent process, identified as a biomarker for physiological aging (GlycoAge Test). To investigate whether traumatic stress accelerates the aging process, we analyzed the N-glycosylation profile in n=13 individuals with PTSD, n=9 trauma-exposed individuals and in n=10 low-stress control subjects. Individuals with PTSD and trauma-exposed individuals presented an upward shift in the GlycoAge Test, equivalent to an advancement of the aging process by 15 additional years. Trauma-exposed individuals presented an intermediate N-glycosylation profile positioned between severely traumatized individuals with PTSD and low-stress control subjects. In conclusion, our data suggest that cumulative exposure to traumatic stressors accelerates the process of physiological aging.
- Published
- 2013
5. N-glycosylation profiling of plasma provides evidence for accelerated physiological aging in post-traumatic stress disorder
- Author
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Moreno-Villanueva, M, primary, Morath, J, additional, Vanhooren, V, additional, Elbert, T, additional, Kolassa, S, additional, Libert, C, additional, Bürkle, A, additional, and Kolassa, I-T, additional
- Published
- 2013
- Full Text
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6. Glycogen and aging: an in vitro model of a new relationship
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Testoni, G., primary, Vanhooren, V., additional, Libert, C., additional, and Guinovart, J., additional
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- 2013
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7. 1021 ALTERATION OF FUCOSYLATED N-GLYCOME IN THE PATIENTS WITH HEPATOCELLULAR CARCINOMA
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Wang, L., primary, Dewaele, S., additional, Vanhooren, V., additional, Liu, X.-E., additional, Libert, C., additional, Lu, F.-M., additional, Zhuang, H., additional, and Chen, C.C., additional
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- 2011
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8. 511 INCREASED SHEAR STRESS ALONE CAN INDUCE HEPATIC PROLIFERATION IN NORMAL LIVERS
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Fan, Y.-D., primary, Chen, C., additional, Meester, D., additional, Van Huysse, J., additional, Dewaele, S., additional, Vanhooren, V., additional, Libert, C., additional, Praet, M., additional, Roels, F., additional, and de Hemptinne, B., additional
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- 2008
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9. N-glycomic changes in serum proteins during human aging.
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Vanhooren V, Desmyter L, Liu X, Cardelli M, Franceschi C, Federico A, Libert C, Laroy W, Dewaele S, Contreras R, and Chen C
- Abstract
N-glycan profiling of the human serum glycoproteins including immunoglobulin fraction on different age groups of healthy persons shows substantial changes with increasing age in three major N-glycan structures. In individuals more than 40-50 years of age, there is an increase in under-galactosylated glycans and a decrease in the core alpha-1,6-fucosylated bi-galactosylated biantennary structure. These three glycan structures are also substantially changed in a Werner syndrome patient, to a level comparable or even more pronounced than those observed in a healthy Italian centenarian population. These data show that the glycosylation machineries in both liver cells and B-cells are affected in a similar way by the aging process despite their highly different nature. The observed changes in the glycan structures are indicative that biosynthetic processes are at the basis of the changes, possibly together with changes in serum clearing of glycan-altered proteins. Our data suggest that measurement of the N-glycan level changes could provide a noninvasive surrogate marker for general health or for age-related disease progression, and for monitoring the improvement of health after therapy. [ABSTRACT FROM AUTHOR]
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- 2007
- Full Text
- View/download PDF
10. [N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus]
- Author
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Xue-en Liu, Desmyter, L., Gao, C. F., Laroy, W., Dewaele, S., Vanhooren, V., Wang, L., Zhuang, H., Callewaert, N., Libert, C., Contreras, R., and Chen, C. Y.
11. Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat
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Fang Meng, Dewaele Sylviane, Zhao Yun-peng, Stärkel Peter, Vanhooren Valerie, Chen Yue-ming, Ji Xin, Luo Ming, Sun Bao-mu, Horsmans Yves, Dell Anne, Haslam Stuart M, Grassi Paola, Libert Claude, Gao Chun-fang, and Chen Cuiying
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background There is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model. Results Rat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory. In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p < 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. Conclusions: We found an increase in core-α-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.
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- 2010
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12. N-glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters
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Claudio Franceschi, Antonio Ceriello, Sylviane Dewaele, Paolo Garagnani, Stefano Salvioli, Valerie Vanhooren, Vincenzo Borelli, Roberto Testa, Maria Giulia Bacalini, Liana Spazzafumo, Fabiola Olivieri, Stefano Genovese, Anna Rita Bonfigli, Claude Libert, Massimo Boemi, Testa R, Vanhooren V, Bonfigli AR, Boemi M, Olivieri F, Ceriello A, Genovese S, Spazzafumo L, Borelli V, Bacalini MG, Salvioli S, Garagnani P, Dewaele S, Libert C, and Franceschi C
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Male ,Glycosylation ,BLOOD ,lcsh:Medicine ,N-glycans ,Type 2 diabetes ,Biology ,DNA-SEQUENCING EQUIPMENT ,GLUCOSE-TRANSPORT ,DISEASE ,chemistry.chemical_compound ,Insulin resistance ,Polysaccharides ,Diabetes mellitus ,O-GLCNAC MODIFICATION ,medicine ,Humans ,lcsh:Science ,Glycomics ,Aged ,Glycoproteins ,chemistry.chemical_classification ,Metabolic Syndrome ,type 2 diabete ,INSULIN-RESISTANCE ,Multidisciplinary ,GLYCOSYLATION ,lcsh:R ,Glucose transporter ,GLYCOPROTEIN ,Type 2 Diabetes Mellitus ,Biology and Life Sciences ,Blood Proteins ,Middle Aged ,medicine.disease ,Blood proteins ,carbohydrates (lipids) ,OLIGOSACCHARIDES ,GLYCAN ,chemistry ,Biochemistry ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,lipids (amino acids, peptides, and proteins) ,Female ,lcsh:Q ,Glycoprotein ,Research Article - Abstract
Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome. Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6 +/- 8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5 +/- 12.4 years). N-glycome was evaluated in serum glycoproteins. Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, alpha(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P
- Published
- 2015
13. N-glycomic biomarkers of biological aging and longevity: A link with inflammaging
- Author
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Manfred Wuhrer, Fabio Dall'Olio, Cuiying Chitty Chen, P. Eline Slagboom, Valerie Vanhooren, Claudio Franceschi, Dall'Olio F., Vanhooren V., Chen C.C., Slagboom P.E., Wuhrer M., and Franceschi C.
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Aging ,Inflammation ,Biology ,Biochemistry ,Progeroid syndromes ,Autoimmune Diseases ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Progeria ,Biomarkers of aging ,INFLAMMATION ,Polysaccharides ,Autoimmune disease ,medicine ,Animals ,Humans ,Rheumatoid arthritis ,Molecular Biology ,Glycomics ,030304 developmental biology ,Mannan-binding lectin ,Aged ,Feedback, Physiological ,0303 health sciences ,GLYCOSYLATION ,Autoantibody ,Complement Pathway, Mannose-Binding Lectin ,Models, Theoretical ,medicine.disease ,Complement system ,High-throughput glycomic analysis ,Neurology ,030220 oncology & carcinogenesis ,Lectin pathway ,Immunoglobulin G ,Immunology ,inflammaging ,medicine.symptom ,Asparagine ,Protein Processing, Post-Translational ,antibody glycosylation ,Biomarkers ,Biotechnology - Abstract
Glycosylation is a frequent co/post-translational modification of proteins which modulates a variety of biological functions. The analysis of N-glycome, i.e. the sugar chains N-linked to asparagine, identified new candidate biomarkers of aging such as N-glycans devoid of galactose residues on their branches, in a variety of human and experimental model systems, such as healthy old people, centenarians and their offspring and caloric restricted mice. These agalactosylated biantennary structures mainly decorate Asn297 of Fc portion of IgG (IgG-G0), and are present also in patients affected by progeroid syndromes and a variety of autoimmune/inflammatory diseases. IgG-G0 exert a pro-inflammatory effect through different mechanisms, including the lectin pathway of complement, binding to Fcgamma receptors and formation of autoantibody aggregates. The age-related accumulation of IgG-G0 can contribute to inflammaging, the low-grade pro-inflammatory status that characterizes elderly, by creating a vicious loop in which inflammation is responsible for the production of aberrantly glycosylated IgG which, in turn, would activate the immune system, exacerbating inflammation. Moreover, recent data suggest that the N-glycomic shift observed in aging could be related not only to inflammation but also to alteration of important metabolic pathways. Thus, altered N-glycans are both powerful markers of aging and possible contributors to its pathogenesis
- Published
- 2013
14. Serum N-glycan profile shift during human ageing
- Author
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Cuiying Chitty Chen, Sylviane Dewaele, Peter Paul De Deyn, Koos Jaspers, Florence Debacq-Chainiaux, Ingrid van der Pluijm, Michel Poulain, Jan H.J. Hoeijmakers, Olivier Toussaint, Sebastiaan Engelborghs, Youri Glupczynski, Claude Libert, Claudio Franceschi, Valerie Vanhooren, Molecular Genetics, Clinical sciences, Neurology, Department for Molecular Biomedical Research, Department of Biomedical Molecular Biology, Universiteit Gent = Ghent University [Belgium] (UGENT), Reference Center for Biological Markers of Memory Disorders, University of Namur - FUNDP / URBC 61, GéDAP - Faculté des sciences économiques, Cliniques universitaires UCL de Mont-Godinne 5530 Yvoir, Dept. Experimental Pathology, Vanhooren V., Dewaele S., Libert C., Engelborghs S., De Deyn P.P., Toussaint O., Debacq-Chainiaux F., Poulain M., Glupczynski Y., Franceschi C., Jaspers K., van der Pluijm I., Hoeijmakers J., and Chen C.C.
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Aging ,Physiology ,NGA2F ,Glycomics/instrumentation ,Disease ,Biochemistry ,Cockayne syndrome ,0302 clinical medicine ,Endocrinology ,Young adult ,Glycomics ,Medicine(all) ,Aged, 80 and over ,0303 health sciences ,NA2F ,Middle Aged ,3. Good health ,Cockayne Syndrome/blood ,Dementia/blood ,Biomarker (medicine) ,CS ,Adult ,Electrophoresis ,Aging/blood ,Biology ,Sensitivity and Specificity ,03 medical and health sciences ,Young Adult ,SDG 3 - Good Health and Well-being ,Polysaccharides ,Genetics ,medicine ,Dementia ,Humans ,Electrophoresis/instrumentation ,Cockayne Syndrome ,Molecular Biology ,030304 developmental biology ,Aged ,age-related disease ,Surrogate endpoint ,Cell Biology ,Biomarker ,Sequence Analysis, DNA ,medicine.disease ,DSA-FACE ,Ageing ,ageing ,Immunology ,Polysaccharides/blood ,N-glycan profile ,Sequence Analysis, DNA/instrumentation ,Human medicine ,Body mass index ,030217 neurology & neurosurgery ,Biomarkers/blood ,Biomarkers - Abstract
Biomarkers indicating biological age are of significant interest for prevention, diagnosis and monitoring (and the treatment) of age-related diseases. We previously reported an alteration of serum N-glycan profile in old humans using "DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis" (DSA-FACE). To validate the shift in serum N-glycan profile during ageing, we studied serum N-glycan profiles in different age groups of healthy volunteers, patients with dementia, and patients with Cockayne syndrome, a genetic DNA repair disorder involving neurodegeneration and premature ageing. We found that the log of the ratio of two glycans (NGA2F and NA2F), named GlycoAgeTest, remained steady up to the age of 40. years and thereafter gradually increased to reach its highest level in nonagenarians. Patients with dementia or Cockayne syndrome had a higher GlycoAgeTest level than age-matched healthy individuals. We thus demonstrate that the value of GlycoAgeTest is better than chronological age for estimating the physiological age of a human individual, and that it could be used as an ageing biomarker for healthy humans. Our data indicate that the GlycoAgeTest could be used as a non-invasive surrogate marker for general health, for forecasting disease progression during ageing, and for monitoring the efficacy of anti-ageing food compounds. © 2010 Elsevier Inc.
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- 2010
15. N-glycan profiles as tools in diagnosis of hepatocellular carcinoma and prediction of healthy human ageing
- Author
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Cuiying Chen, Roland Contreras, Chun Fang Gao, Claude Libert, Claudio Franceschi, Xue-En Liu, Valerie Vanhooren, Vanhooren V., Liu X.E., Franceschi C., Gao C.F., Libert C., Contreras R., and Chen C.
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Adult ,Aging ,Glycan ,Carcinoma, Hepatocellular ,Glycosylation ,Cell ,Biology ,Sensitivity and Specificity ,Genome ,Glycomics ,chemistry.chemical_compound ,Polysaccharides ,Predictive Value of Tests ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Aged, 80 and over ,chemistry.chemical_classification ,Liver Neoplasms ,Blood Proteins ,Middle Aged ,Blood proteins ,carbohydrates (lipids) ,medicine.anatomical_structure ,Enzyme ,ROC Curve ,Biochemistry ,chemistry ,biology.protein ,Glycoprotein ,Developmental Biology - Abstract
Protein glycosylation, the most common form of co-translational modification of proteins, is the enzymatic addition of sugars or oligosaccharides (glycans) to proteins. Protein glycosylation increases the diversity of the functions of proteins encoded in the genome. The result is that different glycomes of the same protein may have different functional, kinetic or physical properties. The glycosylation pathway is largely regulated by the condition of the cells, which means that the sugar chains can be altered by the physiological or pathophysiological condition of the cell. Thus, the type of glycans produced by cells, tissues, or organism could reflect their current physiological state. We determined the N-glycan profiles of serum proteins by using DNA sequencer-based carbohydrate analytical profiling technology. We show that two N-glycan structures (NGA2F and NA2F) present in human blood glycoproteins change with ageing, and that one triantennary glycan (NA3Fb) is correlated with tumor stage in HCC patients. Therefore, examining alterations in serum glycan fingerprint by using our platform could be a suitable tool for monitoring the healthiness of ageing and for the follow-up of pathophysiological conditions such as liver cancer.
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- 2009
16. N-glycomic changes in serum proteins during human aging
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Cuiying Chen, Sylviane Dewaele, Valerie Vanhooren, Antonio Federico, Liesbeth Desmyter, Claudio Franceschi, Maurizio Cardelli, Roland Contreras, Wouter Laroy, Claude Libert, Xue-En Liu, Vanhooren V., Desmyter L., Liu X.E., Cardelli M., Franceschi C., Federico A., Libert C., Laroy W., Dewaele S., Contreras R., and Chen C.
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Male ,Glycan ,Aging ,Glycosylation ,Population ,Physiology ,Immunoglobulins ,chemistry.chemical_compound ,Polysaccharides ,medicine ,Humans ,skin and connective tissue diseases ,education ,Werner syndrome ,Aged ,Glycoproteins ,chemistry.chemical_classification ,Aged, 80 and over ,education.field_of_study ,biology ,Blood Proteins ,medicine.disease ,Blood proteins ,carbohydrates (lipids) ,chemistry ,Immunology ,biology.protein ,Female ,sense organs ,Werner Syndrome ,Geriatrics and Gerontology ,Antibody ,Centenarian ,Glycoprotein - Abstract
N-glycan profiling of the human serum glycoproteins including immunoglobulin fraction on different age groups of healthy persons shows substantial changes with increasing age in three major N-glycan structures. In individuals more than 40-50 years of age, there is an increase in under-galactosylated glycans and a decrease in the core alpha-1,6-fucosylated bi-galactosylated biantennary structure. These three glycan structures are also substantially changed in a Werner syndrome patient, to a level comparable or even more pronounced than those observed in a healthy Italian centenarian population. These data show that the glycosylation machineries in both liver cells and B-cells are affected in a similar way by the aging process despite their highly different nature. The observed changes in the glycan structures are indicative that biosynthetic processes are at the basis of the changes, possibly together with changes in serum clearing of glycan-altered proteins. Our data suggest that measurement of the N-glycan level changes could provide a noninvasive surrogate marker for general health or for age-related disease progression, and for monitoring the improvement of health after therapy.
- Published
- 2007
17. Alterations of the serum N-glycan profile in female patients with Major Depressive Disorder.
- Author
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Boeck C, Pfister S, Bürkle A, Vanhooren V, Libert C, Salinas-Manrique J, Dietrich DE, Kolassa IT, and Karabatsiakis A
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- Aged, Biomarkers blood, C-Reactive Protein analysis, Case-Control Studies, Depressive Disorder, Major complications, Female, Humans, Inflammation complications, Interleukin-6 blood, Middle Aged, Tumor Necrosis Factor-alpha blood, Depressive Disorder, Major blood, Inflammation blood, Polysaccharides blood
- Abstract
Background: Glycans are short chains of saccharides linked to glycoproteins that are known to be involved in a wide range of inflammatory processes. As depression has been consistently associated with chronic low-grade inflammation, we asked whether patients with Major Depressive Disorder show alterations in the N-glycosylation pattern of serum proteins that might be linked to associated changes in inflammatory processes., Methods: In a study cohort of 21 female patients with an acute depressive episode and 21 non-depressed female control subjects aged between 50 and 69 years, we analyzed the serum N-glycan profile by DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis (DSA-FACE) and assessed the serum levels of interleukin (IL)- 6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) by chemiluminescence immunoassays and nephelometry., Results: Compared to controls, MDD patients showed significant differences in the serum levels of several N-glycan structures. Alterations in the serum N-glycan profile were associated with depressive symptom severity and exploratory analyses revealed that they were most pronounced in MDD patients with a history of childhood sexual abuse. Furthermore, MDD patients showed higher levels of IL-6 and a trend for higher CRP levels, which were also associated with similar alterations in the serum N-glycan profile as those characteristic for MDD patients., Limitations: The relatively small sample size and the presence of potential confounders (e.g., BMI, smoking, medication)., Conclusion: The results offer the first evidence that specific differences in the N-glycosylation pattern of serum proteins constitute a so far unrecognized level of biological alterations that might be involved in the immune changes associated with MDD., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2018
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18. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles.
- Author
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Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, Brkic M, Demeestere D, Vanhooren V, Hendrix A, Libert C, and Vandenbroucke RE
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- Animals, Cells, Cultured, Cerebrospinal Fluid chemistry, Epithelial Cells drug effects, Epithelial Cells metabolism, Immunologic Factors metabolism, Lipopolysaccharides metabolism, Mice, Inbred C57BL, MicroRNAs analysis, Organ Culture Techniques, Blood-Brain Barrier pathology, Brain pathology, Choroid Plexus metabolism, Extracellular Vesicles metabolism, Inflammation pathology
- Abstract
Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood-brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)
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- 2016
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19. Preeclampsia transforms membrane N-glycome in human placenta.
- Author
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Robajac D, Vanhooren V, Masnikosa R, Miković Ž, Mandić V, Libert C, and Nedić O
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- Endothelium, Vascular metabolism, Endothelium, Vascular pathology, Female, Glycosylation, Humans, Hypertension metabolism, Pregnancy, Cell Membrane metabolism, Glycoproteins metabolism, Placenta metabolism, Pre-Eclampsia metabolism
- Abstract
Posttranslational modifications (PTM) which accompany pathological conditions affect protein structure, characteristics and modulate its activity. Glycosylation is one of the most frequent PTM influencing protein folding, localisation and function. Hypertension is a common gestational complication, which can lead to foetal growth restriction (IUGR) and even to foetal or maternal death. In this work we focused on the impact of preeclampsia complicated with IUGR on placental membrane N-glycome. Results have shown that preeclampsia reduced fucosylation of placental glycans, increased the appearance of paucimannosidic and mannosidic structures with lower number of mannose residues and decreased the amount of glycans with more mannose residues. Since preeclampsia is tightly connected to IUGR, glycosylation changes were investigated also on the functional membrane receptors responsible for growth: insulin receptor and the type 1 insulin-like growth factor receptor (IR and IGF1R). It was found that IR present in the IUGR placenta contained significantly less α2,6-Sia. Therefore, glycans on placental membranes alter due to preeclampsia, but changes seen at the level of the entire N-glycome may be different from the changes detected at the level of a specific glycoprotein. The difference recorded due to pathology in one membrane molecule (IR) was not found in another homologous molecule (IGF1R). Thus, besides studying the glycosylation pattern of the entire placental membrane due to preeclampsia, it is inevitable to study directly glycoprotein of interest, as no general assumptions or extrapolations can be made., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2016
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20. N-glycome Profile Levels Relate to Silent Brain Infarcts in a Cohort of Hypertensives.
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Vilar-Bergua A, Riba-Llena I, Vanhooren V, Dewaele S, Libert C, Penalba A, Montaner J, and Delgado P
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- Aged, Asymptomatic Diseases, Biomarkers blood, Brain Infarction etiology, Brain Infarction pathology, Chi-Square Distribution, Cohort Studies, Female, Humans, Hypertension complications, Hypertension diagnosis, Leukoencephalopathies etiology, Leukoencephalopathies pathology, Linear Models, Logistic Models, Magnetic Resonance Imaging, Male, Middle Aged, Odds Ratio, Predictive Value of Tests, Risk Factors, Brain Infarction blood, Glycomics methods, Hypertension blood, Leukoencephalopathies blood, Polysaccharides blood
- Abstract
Background: Silent brain infarcts (SBIs) are highly prevalent in the aged population and relate to the occurrence of further stroke and dementia. Serum N-glycome levels have been previously associated with aging and they might be related as well to the presence of SBIs and age-related white matter hyperintensities., Methods and Results: We determined the serum N-glycome profile in a cohort study comprising 972 subjects and evaluated the relationship between N-glycome levels and the presence and number of SBIs and with age-related white matter hyperintensities grades, assessed by brain magnetic resonance imaging. Decreasing concentrations of bigalacto core-α-1,6-fucosylated biantennary glycan and increasing concentrations of branching α-1,3-fucosylated triantennary glycan remained as independent predictors of SBIs (odds ratio 0.4, 95% CI 0.3-0.7 and odds ratio 1.8, 95% CI 1-3.2, respectively), after controlling for the presence of age and classic vascular risk factors. A similar pattern was found to be related to an increasing number of SBIs and white matter hyperintensities grade., Conclusions: N-glycome levels might be potentially useful as biomarkers for the presence of silent cerebrovascular disease., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Published
- 2015
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21. Protein modification and maintenance systems as biomarkers of ageing.
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Vanhooren V, Navarrete Santos A, Voutetakis K, Petropoulos I, Libert C, Simm A, Gonos ES, and Friguet B
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- Animals, Biomarkers metabolism, Humans, Oxidation-Reduction, Longevity physiology, Protein Processing, Post-Translational physiology, Proteolysis
- Abstract
Changes in the abundance and post-translational modification of proteins and accumulation of some covalently modified proteins have been proposed to represent hallmarks of biological ageing. Within the frame of the Mark-Age project, the workpackage dedicated to "markers based on proteins and their modifications" has been firstly focused on enzymatic and non-enzymatic post-translational modifications of serum proteins by carbohydrates. The second focus of the workpackage has been directed towards protein maintenance systems that are involved either in protein quality control (ApoJ/Clusterin) or in the removal of oxidatively damaged proteins through degradation and repair (proteasome and methionine sulfoxide reductase systems). This review describes the most relevant features of these protein modifications and maintenance systems, their fate during ageing and/or their implication in ageing and longevity., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
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- 2015
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22. Plasma N-Glycome Signature of Down Syndrome.
- Author
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Borelli V, Vanhooren V, Lonardi E, Reiding KR, Capri M, Libert C, Garagnani P, Salvioli S, Franceschi C, and Wuhrer M
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- Adolescent, Adult, Aged, Aged, 80 and over, Carbohydrate Metabolism, Carbohydrate Sequence, Case-Control Studies, Child, Down Syndrome pathology, Female, Fucose blood, Fucose chemistry, Galactose blood, Galactose chemistry, Glycosylation, Humans, Male, Middle Aged, Molecular Sequence Data, Mothers, Polysaccharides chemistry, Sialic Acids blood, Sialic Acids chemistry, Siblings, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Aging blood, Down Syndrome blood, Glycomics methods, Polysaccharides blood
- Abstract
In recent years, plasma N-glycans have emerged as biomarkers for health and disease. Here, we studied N-glycomic changes in Down Syndrome (DS). Because of the progeroid phenotype of DS, we focused on the dissection of syndrome- and aging-associated glycomic changes, as well as the interaction thereof. We analyzed the plasma N-glycome of 76 DS persons, 37 siblings (DSS), and 42 mothers (DSM) of DS persons by DNA-sequencer-aided, fluorophore-assisted-carbohydrate-electrophoresis, as well as by matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). The results showed an overall decrease of galactosylation and α2,3 sialylation, a concomitant increase of the level of fucosylated N-glycans as well as of monogalactosylated diantennary N-glycans in DS, while the GlycoAgeTest and the ratio of the two core-fucosylated, monogalactosylated diantennary isomers (galactose positioned on α1,6 arm versus α1,3 arm) were the strongest DS discriminators. Hypogalactosylation is a characteristic of both DS and aging of control individuals. A decrease in α2,3-sialylated species is also common to DS and aging of controls. However, regarding to α2,6-sialylated tri- and tetragalactosylated N-glycan species, we found those to be lowered in DS but showed an increase with age in the same persons, while these glycans were not affected by aging in control individuals. In conclusion, we identified specific glycomic changes associated with DS, aging in DS, as well as aging in controls, identifying glycomic features in line with accelerated aging in DS. Notably, our data demonstrate an aging phenotype in DS which only in part overlaps with aging in controls but reveals DS-specificity.
- Published
- 2015
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23. N-glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters.
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Testa R, Vanhooren V, Bonfigli AR, Boemi M, Olivieri F, Ceriello A, Genovese S, Spazzafumo L, Borelli V, Bacalini MG, Salvioli S, Garagnani P, Dewaele S, Libert C, and Franceschi C
- Subjects
- Aged, Case-Control Studies, Female, Glycoproteins blood, Glycoproteins metabolism, Humans, Male, Middle Aged, Blood Proteins metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Glycomics methods, Metabolic Syndrome complications, Metabolic Syndrome metabolism, Polysaccharides metabolism
- Abstract
Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome., Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6±8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5±12.4 years). N-glycome was evaluated in serum glycoproteins., Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, α(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with α(1,6)- and α(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS)., Conclusions: Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS.
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- 2015
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24. The N-glycan profile of placental membrane glycoproteins alters during gestation and aging.
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Robajac D, Masnikosa R, Vanhooren V, Libert C, Miković Ž, and Nedić O
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- Adult, Electrophoresis, Polyacrylamide Gel methods, Female, Gestational Age, Humans, Maternal Age, Membrane Glycoproteins analysis, Membrane Glycoproteins metabolism, Placentation physiology, Pregnancy, Pregnancy Proteins analysis, Pregnancy Proteins metabolism, Pregnancy Trimesters physiology, Reproducibility of Results, alpha-L-Fucosidase metabolism, alpha-L-Fucosidase pharmacology, Placenta metabolism, Polysaccharides analysis, Polysaccharides metabolism
- Abstract
Alterations in the glycosylation of few membrane proteins from human placenta during gestation have been documented, but data on N-glycome of placental membrane proteins are still missing. The primary goal of this study was to obtain N-glycan profiles of human placental membrane proteins using a reliable, simple and high-throughput method. The second goal was to examine whether the N-glycan profile alters during gestation. Placental membrane proteins were isolated from women of different ages after first and third trimesters of pregnancy. The N-glycan fingerprint of membrane proteins was obtained using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Lectin blotting was used to confirm DSA-FACE results. Observed gestation-related alterations were: greater abundance of core-fucosylated and multiantennary N-glycans, but lower amounts of bisected biantennary N-glycans together with a decrease in α2,3-sialylation. Age-related alterations were: more core Fuc and more α2,3-Sia in first trimester placentas from older women than in those from younger women; also less core Fuc and less α2,6-Sia in third trimester placentas from older women compared to those from younger women. This study represents the first N-glycan profiling of placental cell membrane proteins. These data represent a basis for future research on the N-glycome of placental proteins in different (patho)physiological conditions., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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25. Mice overexpressing β-1,4-Galactosyltransferase I are resistant to TNF-induced inflammation and DSS-induced colitis.
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Vanhooren V, Vandenbroucke RE, Dewaele S, Van Hamme E, Haigh JJ, Hochepied T, and Libert C
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- Animals, Disease Susceptibility, Female, Gene Expression, Humans, Inflammation chemically induced, Inflammation genetics, Intestinal Mucosa drug effects, Intestinal Mucosa microbiology, Mice, Mice, Transgenic, Microbiota drug effects, Phenotype, Colitis chemically induced, Colitis genetics, Dextran Sulfate adverse effects, Galactosyltransferases genetics, Tumor Necrosis Factor-alpha adverse effects
- Abstract
Glycosylation is an essential post-translational modification, which determines the function of proteins and important processes such as inflammation. β-1,4-galactosyltransferase I (βGalT1) is a key enzyme involved in the addition of galactose moieties to glycoproteins. Intestinal mucins are glycoproteins that protect the gut barrier against invading pathogens and determine the composition of the intestinal microbiota. Proper glycosylation of mucus is important in this regard. By using ubiquitously expressing βGalT1 transgenic mice, we found that this enzyme led to strong galactosylation of mucus proteins, isolated from the gut of mice. This galactosylation was associated with a drastic change in composition of gut microbiota, as TG mice had a significantly higher Firmicutes to Bacteroidetes ratio. TG mice were strongly protected against TNF-induced systemic inflammation and lethality. Moreover, βGalT1 transgenic mice were protected in a model of DSS-induced colitis, at the level of clinical score, loss of body weight, colon length and gut permeability. These studies put βGalT1 forward as an essential protective player in exacerbated intestinal inflammation. Optimal galactosylation of N-glycans of mucus proteins, determining the bacterial composition of the gut, is a likely mechanism of this function.
- Published
- 2013
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26. N-glycomic biomarkers of biological aging and longevity: a link with inflammaging.
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Dall'Olio F, Vanhooren V, Chen CC, Slagboom PE, Wuhrer M, and Franceschi C
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- Aged, Animals, Asparagine metabolism, Autoimmune Diseases metabolism, Biomarkers metabolism, Complement Pathway, Mannose-Binding Lectin, Glycomics, Humans, Inflammation metabolism, Mice, Models, Theoretical, Progeria metabolism, Protein Processing, Post-Translational, Aging metabolism, Feedback, Physiological, Glycosylation, Immunoglobulin G metabolism, Polysaccharides metabolism
- Abstract
Glycosylation is a frequent co/post-translational modification of proteins which modulates a variety of biological functions. The analysis of N-glycome, i.e. the sugar chains N-linked to asparagine, identified new candidate biomarkers of aging such as N-glycans devoid of galactose residues on their branches, in a variety of human and experimental model systems, such as healthy old people, centenarians and their offspring and caloric restricted mice. These agalactosylated biantennary structures mainly decorate Asn297 of Fc portion of IgG (IgG-G0), and are present also in patients affected by progeroid syndromes and a variety of autoimmune/inflammatory diseases. IgG-G0 exert a pro-inflammatory effect through different mechanisms, including the lectin pathway of complement, binding to Fcγ receptors and formation of autoantibody aggregates. The age-related accumulation of IgG-G0 can contribute to inflammaging, the low-grade pro-inflammatory status that characterizes elderly, by creating a vicious loop in which inflammation is responsible for the production of aberrantly glycosylated IgG which, in turn, would activate the immune system, exacerbating inflammation. Moreover, recent data suggest that the N-glycomic shift observed in aging could be related not only to inflammation but also to alteration of important metabolic pathways. Thus, altered N-glycans are both powerful markers of aging and possible contributors to its pathogenesis., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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27. The mouse as a model organism in aging research: usefulness, pitfalls and possibilities.
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Vanhooren V and Libert C
- Subjects
- Animals, Caloric Restriction, Crosses, Genetic, Humans, Hypophysectomy, Life Expectancy, Longevity drug effects, Methionine physiology, Mice, Inbred Strains, Mice, Knockout, Mice, Mutant Strains, Models, Biological, Models, Genetic, Reference Values, Research, Aging physiology, Mice physiology
- Abstract
The mouse has become the favorite mammalian model. Among the many reasons for this privileged position of mice is their genetic proximity to humans, the possibilities of genetically manipulating their genomes and the availability of many tools, mutants and inbred strains. Also in the field of aging, mice have become very robust and reliable research tools. Since laboratory mice have a life expectancy of only a few years, genetic approaches and other strategies for intervening in aging can be tested by examining their effects on life span and aging parameters during the relatively short period of, for example, a PhD project. Moreover, experiments on mice with an extended life span as well as on mice demonstrating signs of (segmental) premature aging, together with genetic mapping strategies, have provided novel insights into the fundamental processes that drive aging. Finally, the results of studies on caloric restriction and pharmacological anti-aging treatments in mice have a high degree of relevance to humans. In this paper, we review a number of recent genetic mapping studies that have yielded novel insights into the aging process. We discuss the value of the mouse as a model for testing interventions in aging, such as caloric restriction, and we critically discuss mouse strains with an extended or a shortened life span as models of aging., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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28. Alteration in N-glycomics during mouse aging: a role for FUT8.
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Vanhooren V, Dewaele S, Kuro-O M, Taniguchi N, Dollé L, van Grunsven LA, Makrantonaki E, Zouboulis CC, Chen CC, and Libert C
- Subjects
- Animals, Blood Proteins genetics, Caloric Restriction, Fucose metabolism, Fucosyltransferases genetics, Gene Expression, Glucuronidase genetics, Glycoproteins blood, Glycoproteins genetics, Glycosylation, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor I metabolism, Klotho Proteins, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Polysaccharides genetics, Receptor, IGF Type 1 genetics, Receptor, IGF Type 1 metabolism, Aging, Blood Proteins metabolism, Fucosyltransferases blood, Glucuronidase deficiency, Glycomics methods, Polysaccharides blood, Signal Transduction
- Abstract
We recently reported that N-glycosylation changes during human aging. To further investigate the molecular basis determining these alterations, the aging process in mice was studied. N-glycan profiling of mouse serum glycoproteins in different age groups of healthy C57BL/6 mice showed substantial age-related changes in three major N-glycan structures: under-galactosylated biantennary (NGA2F), biantennary (NA2), and core α-1,6-fucosylated -β-galactosylated biantennary structures (NA2F). Mice defective in klotho gene expression (kl/kl), which have a shortened lifespan, displayed a similar but accelerated trend. Interestingly, the opposite trend was observed in slow-aging Snell Dwarf mice (dw/dw) and in mice fed a calorically restricted diet. We also discovered that increased expression and activity of α-1,6-fucosyltransferase (FUT8) in the liver are strongly linked to the age-related changes in glycosylation and that this increased FUT8 and fucosylation influence IGF-1 signaling. These data demonstrate that the glycosylation machinery in liver cells is significantly affected during aging and that age-related increased FUT8 activity could influence the aging process by altering the sensitivity of the IGF-1R signaling pathway., (© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)
- Published
- 2011
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29. Altered desialylated plasma N-glycan profile in patients with non-small cell lung carcinoma.
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Bartling B, Vanhooren V, Dewaele S, Libert C, Hofmann HS, Haerting J, Nuding S, Silber RE, Simm A, and Chen CC
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- Aged, Carcinoma, Non-Small-Cell Lung diagnosis, Female, Glycomics methods, Humans, Lung Neoplasms diagnosis, Male, Middle Aged, N-Acetylneuraminic Acid chemistry, Neoplasm Staging, Polysaccharides chemistry, Prognosis, ROC Curve, Survival Analysis, Biomarkers, Tumor blood, Carcinoma, Non-Small-Cell Lung blood, Lung Neoplasms blood, Polysaccharides blood
- Abstract
Successful therapy of the non-small cell lung carcinoma (NSCLC) depends on its early detection, and non-invasive detection methods are preferred. As plasma proteins are modified by N-linked glycosylation, we tested the importance of the N-glycan profile in diagnosing and prognosticating NSCLC. We analysed desialylated plasma samples from 75 NSCLC patients, and 71 healthy individuals by the high-throughput DNA sequencer-based carbohydrate analytical profiling technique. We detected alterations in the levels of several N-glycans in NSCLC patients. Total α-1,6-core fucosylated biantennaries (NGA2F, NG1A2F, NA2F) and total bisecting α-1,6-core fucosylated biantennaries (NGA2FB, NA2FB) were reduced in NSCLC patients, whereas the branching α-1,3-fucosylated triantennary N-glycan (NA3FB) was increased. Best diagnostic accuracy was identified for NG1A2F. NSCLC patients with TNM stage I stage did not show further differences, but patients with higher stages did (TNM II to IV). Those patients additionally had a reduced level in the α-1,6-core fucosylated structure NA2F with parallel increase in the non-fucosylated structure NA2. In this regard, NSCLC patients with a relatively low amount of NA2 per NA2F had a better three-year survival than patients with high amount. NSCLC patients show an altered N-glycan profile of plasma proteins that may be regarded as a supportive tool for cancer diagnosis.
- Published
- 2011
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30. Serum N-glycan profile shift during human ageing.
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Vanhooren V, Dewaele S, Libert C, Engelborghs S, De Deyn PP, Toussaint O, Debacq-Chainiaux F, Poulain M, Glupczynski Y, Franceschi C, Jaspers K, van der Pluijm I, Hoeijmakers J, and Chen CC
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers blood, Cockayne Syndrome diagnosis, Dementia diagnosis, Electrophoresis instrumentation, Glycomics instrumentation, Humans, Middle Aged, Sensitivity and Specificity, Sequence Analysis, DNA instrumentation, Young Adult, Aging blood, Cockayne Syndrome blood, Dementia blood, Glycomics methods, Polysaccharides blood
- Abstract
Biomarkers indicating biological age are of significant interest for prevention, diagnosis and monitoring (and the treatment) of age-related diseases. We previously reported an alteration of serum N-glycan profile in old humans using "DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis" (DSA-FACE). To validate the shift in serum N-glycan profile during ageing, we studied serum N-glycan profiles in different age groups of healthy volunteers, patients with dementia, and patients with Cockayne syndrome, a genetic DNA repair disorder involving neurodegeneration and premature ageing. We found that the log of the ratio of two glycans (NGA2F and NA2F), named GlycoAgeTest, remained steady up to the age of 40years and thereafter gradually increased to reach its highest level in nonagenarians. Patients with dementia or Cockayne syndrome had a higher GlycoAgeTest level than age-matched healthy individuals. We thus demonstrate that the value of GlycoAgeTest is better than chronological age for estimating the physiological age of a human individual, and that it could be used as an ageing biomarker for healthy humans. Our data indicate that the GlycoAgeTest could be used as a non-invasive surrogate marker for general health, for forecasting disease progression during ageing, and for monitoring the efficacy of anti-ageing food compounds., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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31. Alteration of N-glycome in diethylnitrosamine-induced hepatocellular carcinoma mice: a non-invasive monitoring tool for liver cancer.
- Author
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Liu XE, Dewaele S, Vanhooren V, Fan YD, Wang L, Van Huysse J, Zhuang H, Contreras R, Libert C, and Chen CC
- Subjects
- Animals, Carcinoma, Hepatocellular chemically induced, Carcinoma, Hepatocellular metabolism, DNA Primers genetics, DNA, Complementary genetics, Diethylnitrosamine toxicity, Electrophoresis methods, Fucosyltransferases metabolism, Liver pathology, Liver Neoplasms, Experimental chemically induced, Liver Neoplasms, Experimental metabolism, Mice, N-Acetylglucosaminyltransferases metabolism, Reverse Transcriptase Polymerase Chain Reaction, Biomarkers, Tumor blood, Carcinoma, Hepatocellular diagnosis, Liver Neoplasms, Experimental diagnosis, Polysaccharides blood, Polysaccharides genetics
- Abstract
Background and Aims: There is a demand for serum markers that can routinely assess the progression of liver cancer. DENA (diethylnitrosamine), a hepatocarcinogen, is commonly used in an experimental mouse model to induce liver cancer that closely mimics a subclass of human hepatocellular carcinoma (HCC). However, blood monitoring of the progression of HCC in mouse model has not yet been achieved. In this report, we studied glycomics during the development of mouse HCC induced by DENA., Methods: Mouse HCC was induced by DENA. Serum N-glycans were profiled using the sequencer assisted-Fluorophore-assisted carbohydrate electrophoresis technique developed in our laboratory. Possible alteration in the transcription of genes relevant to the synthesis of the changed glycans was analysed by real-time polymerase chain reaction., Results: In comparison with the control mice that received the same volume of saline, a tri-antennary glycan (peak 8) and a biantennary glycan (peak 4) in serum total glycans of DENA mice increased gradually but significantly during progression of liver cancer, whereas a core-fucosylated biantennary glycan (peak 6) decreased. Expression of alpha-1,6-fucosyltransferase 8 (Fut8), which is responsible for core fucosylation, decreased in the liver of DENA mice compared with that of age-matched control mice. Likewise, the expression level of Mgat4a, which is responsible for tri-antennary, significantly increased in the liver of DENA mice (P<0.001)., Conclusions: The changes of N-glycan levels in the serum could be used as a biomarker to monitor the progress of HCC and to follow up the treatment of liver tumours in this DENA mouse model.
- Published
- 2010
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32. Altered serum glycomics in Alzheimer disease: a potential blood biomarker?
- Author
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Chen CC, Engelborghs S, Dewaele S, Le Bastard N, Martin JJ, Vanhooren V, Libert C, and De Deyn PP
- Subjects
- Adult, Alzheimer Disease blood, Alzheimer Disease cerebrospinal fluid, Biomarkers blood, Biomarkers cerebrospinal fluid, Carbohydrates blood, Carbohydrates cerebrospinal fluid, Case-Control Studies, Electrophoresis methods, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Alzheimer Disease diagnosis, Biomarkers analysis, Carbohydrates analysis, Glycomics
- Abstract
We investigated whether blood N-glycan changes can be used as a diagnostic biomarker for Alzheimer disease (AD). We used DNA sequencer-assisted, fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology to assay N-glycans in sera from 79 autopsy-confirmed dementia patients and 149 healthy controls. One N-glycan (NA2F) was substantially decreased in AD patients but not in controls. Use of NA2F for discriminating AD between dementia patients and healthy controls showed a diagnostic accuracy of 85.7% +/- 2.8% with 92% specificity and 70% sensitivity. The decrease in the level of NA2F in AD patients compared to non-AD patients was more pronounced in females (p < 0.0001) than in males (p < 0.014). Use of NA2F to differentiate female AD from female non-AD patients reached a diagnostic accuracy of 90.7% +/- 4.8 %. Pearson correlation analysis showed that in female dementia patients, serum NA2F levels were significantly correlated with the cerebrospinal fluid (CSF) beta-amyloid peptide of 42 amino acids (Abeta(1-42)) and tau phosphorylated at threonine 181 (P-tau(181P)) levels, whereas in male dementia patients serum NA2F levels were significantly correlated only with CSF total tau protein (T-tau) level. Thus, we suggest that the serum N-glycan marker might be suitable for longitudinal and follow-up studies.
- Published
- 2010
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33. Serum protein N-glycans profiling for the discovery of potential biomarkers for nonalcoholic steatohepatitis.
- Author
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Chen C, Schmilovitz-Weiss H, Liu XE, Pappo O, Halpern M, Sulkes J, Braun M, Cohen M, Barak N, Tur-Kaspa R, Vanhooren V, Van Vlierberghe H, Libert C, Contreras R, and Ben-Ari Z
- Subjects
- Carbohydrate Conformation, Carbohydrate Sequence, Diagnosis, Differential, Fatty Liver diagnosis, Fatty Liver pathology, Humans, Inflammation metabolism, Inflammation pathology, Molecular Sequence Data, ROC Curve, Biomarkers blood, Biomarkers chemistry, Fatty Liver blood, Polysaccharides blood, Polysaccharides chemistry
- Abstract
The hepatic histology in nonalcoholic fatty liver disease can vary from isolated hepatic steatosis to steatohepatitis can progress to cirrhosis and liver-related death. The aim was to evaluate the use of blood serum N-glycan fingerprinting as a tool for differential diagnosis of nonalcoholic steatohepatitis from steatosis. A group of 47 patients with NAFLD was diagnosed by clinical laboratory analysis and ultrasonography, and was studied histologically using the Brunt's scoring system. The control group included 13 healthy individuals. N-glycan profiles of serum proteins were determined by DNA sequencer-based carbohydrate analytical profiling. We have found that the concentrations of two glycans (NGA2F and NA2) and their logarithm ratio of NGA2F versus NA2 (named GlycoNashTest) were associated with the degree of NASH-related fibrosis, but had no correlation with the grade of inflammation nor steatosis severity. When used to screen NAFLD patients, GlycoNashTest could identify advanced NASH-related fibrosis (F3-F4) with the diagnosis sensitivity of 89.5% and specificity of 71.4%. The serum N-glycan profile is a promising noninvasive method for detecting NASH or NASH-related fibrosis in NAFLD patients, which could be a valuable supplement to other markers currently used in diagnosis of NASH.
- Published
- 2009
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34. N-glycan profiles as tools in diagnosis of hepatocellular carcinoma and prediction of healthy human ageing.
- Author
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Vanhooren V, Liu XE, Franceschi C, Gao CF, Libert C, Contreras R, and Chen C
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Blood Proteins metabolism, Glycomics, Glycosylation, Humans, Middle Aged, Predictive Value of Tests, ROC Curve, Sensitivity and Specificity, Aging metabolism, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular metabolism, Liver Neoplasms diagnosis, Liver Neoplasms metabolism, Polysaccharides metabolism
- Abstract
Protein glycosylation, the most common form of co-translational modification of proteins, is the enzymatic addition of sugars or oligosaccharides (glycans) to proteins. Protein glycosylation increases the diversity of the functions of proteins encoded in the genome. The result is that different glycomes of the same protein may have different functional, kinetic or physical properties. The glycosylation pathway is largely regulated by the condition of the cells, which means that the sugar chains can be altered by the physiological or pathophysiological condition of the cell. Thus, the type of glycans produced by cells, tissues, or organism could reflect their current physiological state. We determined the N-glycan profiles of serum proteins by using DNA sequencer-based carbohydrate analytical profiling technology. We show that two N-glycan structures (NGA2F and NA2F) present in human blood glycoproteins change with ageing, and that one triantennary glycan (NA3Fb) is correlated with tumor stage in HCC patients. Therefore, examining alterations in serum glycan fingerprint by using our platform could be a suitable tool for monitoring the healthiness of ageing and for the follow-up of pathophysiological conditions such as liver cancer.
- Published
- 2009
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35. Over-expression of heat shock protein 70 in mice is associated with growth retardation, tumor formation, and early death.
- Author
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Vanhooren V, Liu XE, Desmyter L, Fan YD, Vanwalleghem L, Van Molle W, Dewaele S, Praet M, Contreras R, Libert C, and Chen C
- Subjects
- Animals, Caspase 9 genetics, Caspase 9 metabolism, Cell Death, Corticosterone blood, Female, Gene Expression, HSP70 Heat-Shock Proteins metabolism, Insulin-Like Growth Factor I metabolism, Male, Mice, Mice, Transgenic, Neoplasms, Experimental genetics, Neoplasms, Experimental metabolism, Growth Disorders etiology, HSP70 Heat-Shock Proteins genetics, Neoplasms, Experimental etiology
- Abstract
Experiments in lower organisms, such as worms and flies, indicate that the molecular chaperone protein heat shock protein 70 (HSP70) is a longevity factor. In contrast, we demonstrate here that mice overexpressing HSP70 display growth retardation and early death. HSP70 transgenic mice displayed increased levels of serum corticosterone and weaker expression and activity of the glucocorticoid receptor in the liver. Serum insulin-like growth factor-1 (IGF-1) concentrations in the transgenic mice were 50% lower than in the control mice, leading to growth retardation. HSP70 transgenic mice showed decreased expression of Casp9, which encodes caspase-9, and increased expression of the anti-apoptotic Bcl-2 gene, indicating that apoptosis is suppressed. Consequently, most of the transgenic animals died before the age of 18 months from tumors in their lungs and lymph nodes. We suggest that the proinflammatory and antiapoptotic effects of HSP70 might be responsible for the growth retardation, tumor formation, and early death observed in the HSP70 transgenic mice.
- Published
- 2008
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36. N-glycan profiling in the study of human aging.
- Author
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Vanhooren V, Laroy W, Libert C, and Chen C
- Subjects
- Electrophoresis instrumentation, Glycomics, Humans, Aging blood, Electrophoresis methods, Polysaccharides analysis, Serum chemistry
- Abstract
Most secreted proteins produced by the human body are modified by glycosylation. It is well known that the oligosaccharides (glycans) of glycoproteins are important for initiation of various cellular recognition signals that are essential for the maintenance of the ordered social life of each cell within a multi-cellular organism. The sugar chains can be altered by the physiological or pathophysiological condition of the cell. We describe a detailed protocol for the analysis of N-linked glycans in blood via DNA sequencing equipment-Fluorophore Assisted Carbohydrate Electrophoresis (DSA-FACE). The key features of this technique are its robustness, high throughput, high sensitivity and reliable quantification. Based on DSA-FACE technology, we previously reported that N-glycan profiling of the human serum shows substantial changes with increasing age in three major N-glycan structures. We proposed that measurement of the N-glycan level changes could provide a surrogate marker for general health or for age-related disease progression, and for monitoring the improvement of health after therapy.
- Published
- 2008
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37. [N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus].
- Author
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Liu XE, Desmyter L, Gao CF, Laroy W, Dewaele S, Vanhooren V, Wang L, Zhuang H, Callewaert N, Libert C, Contreras R, and Chen CY
- Subjects
- Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular virology, Hepatitis B virus, Hepatitis B, Chronic blood, Humans, Liver Cirrhosis complications, Liver Cirrhosis virology, Liver Neoplasms complications, Liver Neoplasms virology, Neoplasm Staging, Carcinoma, Hepatocellular blood, Glycomics, Liver Cirrhosis blood, Liver Neoplasms blood
- Published
- 2008
38. N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus.
- Author
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Liu XE, Desmyter L, Gao CF, Laroy W, Dewaele S, Vanhooren V, Wang L, Zhuang H, Callewaert N, Libert C, Contreras R, and Chen C
- Subjects
- Adult, Carcinoma, Hepatocellular pathology, Female, Hepatitis B complications, Humans, Liver Cirrhosis virology, Liver Neoplasms pathology, Male, Middle Aged, Molecular Structure, Neoplasm Staging, Polysaccharides chemistry, alpha-Fetoproteins metabolism, Biomarkers, Tumor blood, Carcinoma, Hepatocellular blood, Liver Cirrhosis blood, Liver Neoplasms blood, Polysaccharides blood
- Abstract
Unlabelled: We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by alpha-fetoprotein (AFP) analysis, ultrasonography, and/or computed tomography and was studied histologically. N-glycan profiles of serum proteins were determined with DNA sequencer-based carbohydrate analytical profiling technology. In this study, we found that a branch alpha(1,3)-fucosylated triantennary glycan was more abundant in patients with HCC than in patients with cirrhosis, patients with fibrosis, and healthy blood donors, whereas a bisecting core alpha(1,6)-fucosylated biantennary glycan was elevated in patients with cirrhosis. The concentration of these 2 glycans and the log ratio of peak 9 to peak 7 (renamed the GlycoHCCTest) were associated with the tumor stage. Moreover, for screening patients with HCC from patients with cirrhosis, the overall sensitivity and specificity of the GlycoHCCTest were very similar to those of AFP., Conclusion: This study indicates that a branch alpha(1,3)-fucosylated glycan is associated with the development of HCC. The serum N-glycan profile is a promising noninvasive method for detecting HCC in patients with cirrhosis and could be a valuable supplement to AFP in the diagnosis of HCC in HBV-infected patients with liver cirrhosis. Its use for the screening, follow-up, and management of patients with cirrhosis and HCC should be evaluated further.
- Published
- 2007
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