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Dermatan sulfate

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https://www.readbyqxmd.com/read/28502917/the-role-of-heparin-cofactor-%C3%A2-in-the-regulation-of-insulin-sensitivity-and-maintenance-of-glucose-homeostasis-in-humans-and-mice
#1
Kiyoe Kurahashi, Seika Inoue, Sumiko Yoshida, Yasumasa Ikeda, Kana Morimoto, Ryoko Uemoto, Kazue Ishikawa, Takeshi Kondo, Tomoyuki Yuasa, Itsuro Endo, Masato Miyake, Seiichi Oyadomari, Toshio Matsumoto, Masahiro Abe, Hiroshi Sakaue, Ken-Ichi Aihara
AIM: Accelerated thrombin action is associated with insulin resistance. It is known that upon activation by binding to dermatan sulfate proteoglycans, heparin cofactor Ⅱ(HCⅡ) inactivates thrombin in tissues. Because HCⅡ may be involved in glucose metabolism, we investigated the relationship between plasma HCⅡ activity and insulin resistance. METHODS AND RESULTS: In a clinical study, statistical analysis was performed to examine the relationships between plasma HCⅡ activity, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and homeostasis model assessment-insulin resistance (HOMA-IR) in elderly Japanese individuals with lifestyle-related diseases...
May 15, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28502328/the-association-between-endocan-levels-and-subclinical-atherosclerosis-in-patients-with-type-2-diabetes-mellitus
#2
Yaya Lv, Yaqiong Zhang, Weiya Shi, Juxiang Liu, Yonghong Li, Zubang Zhou, Qijuan He, Suhong Wei, Jing Liu, Jinxing Quan
BACKGROUND: Proinflammatory conditions induced by circulating factors in diabetes play a pivotal role in endothelial dysfunction and related vascular complications. Endothelial cell-specific molecule-1 or endocan is a dermatan sulfate proteoglycan secreted primarily by the vascular endothelium. Although endocan has been shown to be a potential biomarker in coronary heart disease, its role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In this study, we investigated the correlation between serum endocan levels and subclinical AS in patients with type 2 diabetes mellitus (T2DM)...
May 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28486420/a-fluorescent-probe-for-glycosaminoglycans-applied-to-the-detection-of-dermatan-sulfate-by-a-mix-and-read-assay
#3
Melissa Rappold, Ulrich Warttinger, Roland Krämer
Glycosaminoglycans are complex biomolecules of great biological and medical importance. The quantification of glycosaminoglycans, in particular in complex matrices, is challenging due to their inherent structural heterogeneity. Heparin Red, a polycationic, fluorescent perylene diimide derivative, has recently emerged as a commercial probe for the convenient detection of heparins by a mix-and-read fluorescence assay. The probe also detects glycosaminoglycans with a lower negative charge density than heparin, although with lower sensitivity...
May 9, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28478695/prevention-of-neurocognitive-deficiency-in-mucopolysaccharidosis-type-ii-mice-by-cns-directed-aav9-mediated-iduronate-sulfatase-gene-transfer
#4
Kanut Laoharawee, Kelly M Podetz-Pedersen, Tam T Nguyen, Laura B Evenstar, Kelley F Kitto, Zhenhong Nan, Carolyn A Fairbanks, Walter C Low, Karen F Kozarsky, R Scott McIvor
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked recessive lysosomal disorder caused by defective Iduronate-2-sulfatase (IDS) resulting in accumulation of heparan sulfate and dermatan sulfate glycosaminoglycans (GAGs). Enzyme replacement is the only FDA-approved therapy available for MPS II, but it is expensive and does not improve neurologic outcomes in MPS II patients. We conducted this study to evaluate the effectiveness of adeno-associated virus (AAV) vector encoding human IDS delivered intracerebroventricularly in a murine model of MPS II...
May 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28457718/the-effect-of-galsulfase-enzyme-replacement-therapy-on-the-growth-of-patients-with-mucopolysaccharidosis-vi-maroteaux-lamy-syndrome
#5
P Harmatz, C J Hendriksz, C Lampe, J J McGill, R Parini, E Leão-Teles, V Valayannopoulos, T J Cole, R Matousek, S Graham, N Guffon, A Quartel
Mucopolysaccharidosis (MPS) VI is an autosomal recessive lysosomal storage disorder arising from deficient activity of N-acetylgalactosamine-4-sulfatase (arylsulfatase B) and subsequent intracellular accumulation of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin-4-sulfate. Manifestations are multi-systemic and include skeletal abnormalities such as dysostosis multiplex and short stature. Reference height-for-age growth charts for treatment-naïve MPS VI patients have been published for both the slowly and rapidly progressing populations...
March 31, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28432120/two-glycosaminoglycan-binding-domains-of-the-mouse-cytomegalovirus-encoded-chemokine-mck-2-are-critical-for-oligomerization-of-the-full-length-protein
#6
Sergio M Pontejo, Philip M Murphy
Chemokines are essential for antimicrobial host defenses and tissue repair. Herpesviruses and poxviruses also encode chemokines, copied from their hosts and repurposed for multiple functions, including immune evasion. The CC chemokine MCK-2 encoded by mouse cytomegalovirus (MCMV) has an atypical structure consisting of a classic chemokine domain N-terminal to a second unique domain, resulting from the splicing of MCMV ORFs m131 and m129. MCK-2 is essential for full MCMV infectivity in macrophages and for persistent infection in the salivary gland...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28412940/absence-of-the-dermatan-sulfate-chain-of-decorin-does-not-affect-mouse-development
#7
Pierre Moffatt, Yeqing Geng, Lisa Lamplugh, Antonio Nanci, Peter J Roughley
BACKGROUND: In vitro studies suggest that the multiple functions of decorin are related to both its core protein and its dermatan sulfate chain. To determine the contribution of the dermatan sulfate chain to the functional properties of decorin in vivo, a mutant mouse whose decorin lacked a dermatan sulfate chain was generated. RESULTS: Homozygous mice expressing only the decorin core protein developed and grew in a similar manner to wild type mice. In both embryonic and postnatal mice, all connective tissues studied, including cartilage, skin and cornea, appeared to be normal upon histological examination, and their collagen fibrils were of normal diameter and organization...
April 17, 2017: Journal of Negative Results in Biomedicine
https://www.readbyqxmd.com/read/28401457/comparative-studies-of-vertebrate-iduronate-2-sulfatase-ids-genes-and-proteins-evolution-of-a-mammalian-x-linked-gene
#8
REVIEW
Roger S Holmes
IDS is responsible for the lysosomal degradation of heparan sulfate and dermatan sulfate and linked to an X-linked lysosomal storage disease, mucopolysaccharidosis 2 (MPS2), resulting in neurological damage and early death. Comparative IDS amino acid sequences and structures and IDS gene locations were examined using data from several vertebrate genome projects. Vertebrate IDS sequences shared 60-99% identities with each other. Human IDS showed 47% sequence identity with fruit fly (Drosophila melanogaster) IDS...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28353658/development-of-a-glycosaminoglycan-derived-selectin-targeting-anti-adhesive-coating-to-treat-endothelial-cell-dysfunction
#9
James R Wodicka, Andrea M Chambers, Gurneet S Sangha, Craig J Goergen, Alyssa Panitch
Endothelial cell (EC) dysfunction is associated with many disease states including deep vein thrombosis (DVT), chronic kidney disease, sepsis and diabetes. Loss of the glycocalyx, a thin glycosaminoglycan (GAG)-rich layer on the EC surface, is a key feature of endothelial dysfunction and increases exposure of EC adhesion molecules such as selectins, which are involved in platelet binding to ECs. Once bound, platelets cause thrombus formation and an increased inflammatory response. We have developed a GAG derived, selectin targeting anti-adhesive coating (termed EC-SEAL) consisting of a dermatan sulfate backbone and multiple selectin-binding peptides designed to bind to inflamed endothelium and prevent platelet binding to create a more quiescent endothelial state...
March 29, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28346368/pathophysiological-significance-of-dermatan-sulfate-proteoglycans-revealed-by-human-genetic-disorders
#10
REVIEW
Shuji Mizumoto, Tomoki Kosho, Shuhei Yamada, Kazuyuki Sugahara
The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs) have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity...
March 27, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28297651/glycan-determinants-of-heparin-tau-interaction
#11
Jing Zhao, Isabelle Huvent, Guy Lippens, David Eliezer, Anqiang Zhang, Quanhong Li, Peter Tessier, Robert J Linhardt, Fuming Zhang, Chunyu Wang
Tau aggregates into paired helical filaments within neurons, a pathological hallmark of Alzheimer's disease. Heparin promotes tau aggregation and recently has been shown to be involved in the cellular uptake of tau aggregates. Although the tau-heparin interaction has been extensively studied, little is known about the glycan determinants of this interaction. Here, we used surface plasmon resonance (SPR) and NMR spectroscopy to characterize the interaction between two tau fragments, K18 and K19, and several polysaccharides, including heparin, heparin oligosaccharides, chemically modified heparin, and related glycans...
March 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28246172/a-mammalian-homolog-of-the-zebrafish-transmembrane-protein-2-tmem2-is-the-long-sought-after-cell-surface-hyaluronidase
#12
Hayato Yamamoto, Yuki Tobisawa, Toshihiro Inubushi, Fumitoshi Irie, Chikara Ohyama, Yu Yamaguchi
Hyaluronan (HA) is an extremely large polysaccharide (glycosaminoglycan) involved in many cellular functions. HA catabolism is thought to involve the initial cleavage of extracellular high-molecular-weight (HMW) HA into intermediate-size HA by an extracellular or cell-surface hyaluronidase, internalization of intermediate-size HA, and complete degradation into monosaccharides in lysosomes. Despite considerable research, the identity of the hyaluronidase responsible for the initial HA cleavage in the extracellular space remains elusive...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28238810/defect-in-dermatan-sulfate-in-urine-of-patients-with-ehlers-danlos-syndrome-caused-by-a-chst14-d4st1-deficiency
#13
Shuji Mizumoto, Tomoki Kosho, Atsushi Hatamochi, Tomoko Honda, Tomomi Yamaguchi, Nobuhiko Okamoto, Noriko Miyake, Shuhei Yamada, Kazuyuki Sugahara
PURPOSE: Dermatan sulfate (DS) plays a number of roles in a wide range of biological activities such as cell signaling and tissue morphogenesis through interactions with various extracellular matrix proteins including collagen. Mutations in the carbohydrate sulfotransferase 14 gene (CHST14) encoding CHST14/dermatan 4-O-sulfotransferase-1 (D4ST1), which is responsible for the biosynthesis of DS, cause a recently delineated form of Ehlers-Danlos syndrome (EDS, musculocontractural type 1), an autosomal recessive connective tissue disorder characterized by congenital malformations (specific craniofacial features, and congenital multiple contractures) and progressive fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; and large subcutaneous hematomas)...
February 23, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28207930/elevation-of-glycosaminoglycans-in-the-amniotic-fluid-of-a-fetus-with-mucopolysaccharidosis-vii
#14
Francyne Kubaski, Ana Carolina Brusius-Facchin, Robert W Mason, Pravin Patel, Maira G Burin, Kristiane Michelin-Tirelli, Rejane Gus Kessler, Fernanda Bender, Sandra Leistner-Segal, Carolina A Moreno, Denise P Cavalcanti, Roberto Giugliani, Shunji Tomatsu
OBJECTIVE: The aim of this study was to quantify glycosaminoglycans (GAGs) in amniotic fluid (AF) from an MPS VII fetus compared with age-matched fetuses obtained from normal pregnancies. METHOD: Disaccharides were measured by liquid chromatography tandem mass spectrometry, compared to age-matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes. GUSB was analyzed by next generation sequencing using Ion Torrent Personal Genome Machine with a customized panel...
May 2017: Prenatal Diagnosis
https://www.readbyqxmd.com/read/28199387/dermatan-sulfate-is-a-player-in-the-transglutaminase-2-interaction-network
#15
Grzegorz Wisowski, Ewa M Koźma, Tomasz Bielecki, Adam Pudełko, Krystyna Olczyk
Transglutaminase 2 (TG2) is a multifunctional protein that is primarily engaged in cell adhesion/signaling or shows Ca2+-dependent transglutaminase activity in the extracellular space of tissues. This latter action leads to the cross-linking of the extracellular matrix (ECM) proteins. The enhanced extracellular expression of TG2 is associated with processes such as wound healing, fibrosis or vascular remodeling that are also characterized by a high deposition of dermatan sulfate (DS) proteoglycans in the ECM...
2017: PloS One
https://www.readbyqxmd.com/read/28170539/objective-quantification-of-changes-in-corneal-clouding-over-time-in-patients-with-mucopolysaccharidosis
#16
Ahmed Javed, Tariq Aslam, Simon A Jones, Jane Ashworth
Purpose: We determine objective changes in corneal opacification levels over time in patients with mucopolysaccharidoses (MPS) treated with enzyme replacement therapy or hematopoietic stem cell transplant. A prospective cohort study was done of 9 patients with MPS I (Hurler) or VI (Maroteaux-Lamy). Methods: Quantification of corneal clouding using the Iris camera and full ophthalmic examination, including subjective assessment of corneal clouding, was done in 2011 and repeated in 2015/2016...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28130266/a-potential-role-for-chondroitin-sulfate-dermatan-sulfate-in-arm-regeneration-in-amphiura-filiformis
#17
Rashmi Ramachandra, Ramesh B Namburi, Sam T Dupont, Olga Ortega-Martinez, Toin H van Kuppevelt, Ulf Lindahl, Dorothe Spillmann
Glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) and dermatan sulfate (DS) from various vertebrate and invertebrate sources are known to be involved in diverse cellular mechanisms during repair and regenerative processes. Recently, we have identified CS/DS as the major GAG in the brittlestar Amphiura filiformis, with high proportions of di- and tri-O-sulfated disaccharide units. As this echinoderm is known for its exceptional regeneration capacity, we aimed to explore the role of these GAG chains during A...
May 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28115521/platelet-factor-4-binds-to-vascular-proteoglycans-and-controls-both-growth-factor-activities-and-platelet-activation
#18
Megan S Lord, Bill Cheng, Brooke L Farrugia, Simon McCarthy, John M Whitelock
Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28107390/melanoma-cell-adhesion-and-migration-is-modulated-by-the-uronyl-2-o-sulfotransferase
#19
Katerina Nikolovska, Dorothe Spillmann, Jörg Haier, Andrea Ladányi, Christian Stock, Daniela G Seidler
Although the vast majority of melanomas are characterized by a high metastatic potential, if detected early, melanoma can have a good prognostic outcome. However, once metastasised, the prognosis is bleak. We showed previously that uronyl-2-O sulfotransferase (Ust) and 2-O sulfation of chondroitin/dermatan sulfate (CS/DS) are involved in cell migration. To demonstrate an impact of 2-O sulfation in metastasis we knocked-down Ust in mouse melanoma cells. This significantly reduced the amount of Ust protein and enzyme activity...
2017: PloS One
https://www.readbyqxmd.com/read/28101951/rigidity-and-flexibility-in-the-tetrasaccharide-linker-of-proteoglycans-from-atomic-resolution-molecular-simulation
#20
Cathy Ng, Padmavathy Nandha Premnath, Olgun Guvench
Proteoglycans (PGs) are covalent conjugates between protein and carbohydrate (glycosaminoglycans). Certain classes of glycosaminoglycans such as chondroitin sulfate/dermatan sulfate and heparan sulfate utilize a specific tetrasaccharide linker for attachment to the protein component: GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-Ser. Toward understanding the conformational preferences of this linker, the present work used all-atom explicit-solvent molecular dynamics (MD) simulations combined with Adaptive Biasing Force (ABF) sampling to determine high-resolution, high-precision conformational free energy maps ΔG(φ, ψ) for each glycosidic linkage between constituent disaccharides, including the variant where GlcA is substituted with IdoA...
January 19, 2017: Journal of Computational Chemistry
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