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Heparan sulfate

Arne O Melleby, Mari E Strand, Andreas Romaine, Kate M Herum, Biljana Skrbic, Christen P Dahl, Ivar Sjaastad, Arnt E Fiane, Jorge Filmus, Geir Christensen, Ida G Lunde
Pressure overload is a frequent cause of heart failure. Heart failure affects millions of patients worldwide and is a major cause of morbidity and mortality. Cell surface proteoglycans are emerging as molecular players in cardiac remodeling, and increased knowledge about their regulation and function is needed for improved understanding of cardiac pathogenesis. Here we investigated glypicans (GPC1-6), a family of evolutionary conserved heparan sulfate proteoglycans anchored to the extracellular leaflet of the cell membrane, in experimental and clinical heart failure, and explored the function of glypican-6 in cardiac cells in vitro...
2016: PloS One
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
Ralph D Sanderson, Michael Elkin, Alan C Rapraeger, Neta Ilan, Israel Vlodavsky
Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via non-enzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
Yin Chen, Megan Reddy, Yanlei Yu, Fuming Zhang, Robert J Linhardt
Glycosaminoglycans (GAGs) were prepared from the muscular stomach or gizzard of the chicken. The content of GAGs on a dry weight basis contains 0.4 wt.% a typical value observed for a muscle tissue. The major GAG components were chondroitin-6-sulfate and chondroitin-4-sulfate (~64 %) of molecular weight 21-22 kDa. Hyaluronan (~24 %) had a molecular weight 120 kDa. Smaller amounts (12 %) of heparan sulfate was also present which was made of more highly sulfated chains of molecular weight of 21-22 kDa and a less sulfated low molecular weight (< 10 kDa) heterogeneous partially degraded heparan sulfate...
October 17, 2016: Glycoconjugate Journal
Joanna Majerczak, Marcin Grandys, Krzysztof Duda, Agnieszka Zakrzewska, Aneta Balcerczyk, Leszek Kolodziejski, Dorota Szymoniak-Chochol, Ryszard T Smolenski, Grzegorz Bartosz, Stefan Chlopicki, Jerzy A Zoladz
In this study we have evaluated the effect of 20-weeks of moderate-intensity endurance training (ET) on the endothelial glycocalyx layer integrity in relation to the training-induced changes in antioxidant defence. Eleven healthy young, untrained men performed an incremental cycling exercise until exhaustion before and after 20 weeks of ET. Endurance training consisted of 40- minute sessions, mainly of moderate-intensity (∼50% of VO2max ), performed 4 times per week. Venous blood samples were taken at rest and at the end of the maximal exercise test...
October 17, 2016: Experimental Physiology
Xiao-Jun Chen, Hong Zhang, Zhi-Ping Tan, Wen Hu, Yi-Feng Yang
Multiple osteochondromas (MO), also known as hereditary multiple exostoses, is an autosomal dominant bone disorder. Mutations in exostosin glycosyl transferase‑1 (EXT1) and exostosin glycosyl transferase‑2 (EXT2), including missense, nonsense, frameshift and splice‑site mutations, account for up to 80% of reported cases. The proteins EXT1 and EXT2 form a hetero‑oligomeric complex that functions in heparan sulfate proteoglycan biosynthesis. A heterozygous EXT2 mutation, c.939+1G>T, was identified in a five‑generation 33‑member MO family, and was present in all 13 affected members...
October 6, 2016: Molecular Medicine Reports
Manuela Viola, Kathrin Brüggemann, Evgenia Karousou, Ilaria Caon, Elena Caravà, Davide Vigetti, Burkhard Greve, Christian Stock, Giancarlo De Luca, Alberto Passi, Martin Götte
Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates...
October 15, 2016: Glycoconjugate Journal
Yanlei Yu, Yin Chen, Paiyz Mikael, Fuming Zhang, Apryll M Stalcup, Rebecca German, Francois Gould, Jocelyn Ohlemacher, Hong Zhang, Robert J Linhardt
Heparin, a member of a family of molecules called glycosaminoglycans, is biosynthesized in mucosal mast cells. This important anticoagulant polysaccharide is primarily produced by extraction of the mast cell-rich intestinal mucosa of hogs. There is concern about our continued ability to supply sufficient heparin to support the worldwide growth of advanced medical procedures from the static population of adult hogs used as food animals. While the intestinal mucosa of adult pigs is rich in anticoagulant heparin (containing a few hundred milligrams per animal), little is known about how the content of heparin changes with animal age...
October 15, 2016: Glycobiology
Yury A Bochkov, Kelly Watters, Sarmila Basnet, Shakher Sijapati, Marchel Hill, Ann C Palmenberg, James E Gern
Viruses in the rhinovirus C species (RV-C) can cause severe respiratory illnesses in children including pneumonia and asthma exacerbations. A transduced cell line (HeLa-E8) stably expressing the CDHR3-Y529 receptor variant, supports propagation of RV-C after infection. C15 clinical or recombinant isolates replicate in HeLa-E8, however progeny yields are lower than those of related strains of RV-A and RV-B. Serial passaging of C15 in HeLa-E8 resulted in stronger cytopathic effects and increased (≥10-fold) virus binding to cells and progeny yields...
October 13, 2016: Virology
Francesca Maccari, Fabio Galeotti, Lucia Zampini, Lucia Padella, Rosella Tomanin, Daniela Concolino, Agata Fiumara, Tiziana Galeazzi, Giovanni Coppa, Orazio Gabrielli, Nicola Volpi
BACKGROUND: Urine are easily accessible and relatively simple to process and uronic acid-bearing glycosaminoglycans (UA-GAGs) may serve as biomarkers for several diseases, like for mucopolysaccharidosis. METHODS: We report a study from a large cohort of healthy newborns of 2-3days to have a basic profile of total content of urinary UA-GAGs, their composition and structural signatures utilizing a rapid extractive method and sensitive separation of enzymatic released disaccharides by capillary electrophoresis-light induced fluorescence...
October 11, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Harvy Mauricio Velasco, Yasmin Sanchez, Angela Milena Martin, Luis A Umaña
Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive disorder characterized by impairment in the degradation of Heparan sulfate. Here the authors describe the natural history of 5 related individuals; all associated through a large pedigree which reports a total of 11 affected members, originally from the Boyacá region in Colombia, diagnosed with MPS IIIC who all harbor a novel mutation in HGSNAT The authors report an unusually high incidence of the disease in this population. The clinical features are similar to previously described patients, although some differences in the degree of severity and end-stage of the disease are seen in this specific group...
October 12, 2016: Journal of Child Neurology
Francyne Kubaski, Robert W Mason, Akiko Nakatomi, Haruo Shintaku, Li Xie, Naomi N van Vlies, Heather Church, Roberto Giugliani, Hironori Kobayashi, Seiji Yamaguchi, Yasuyuki Suzuki, Tadao Orii, Toshiyuki Fukao, Adriana M Montaño, Shunji Tomatsu
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. METHODS: This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II...
October 7, 2016: Journal of Inherited Metabolic Disease
Yukinori Endo, Hiroko Ishiwata-Endo, Kenneth M Yamada
Anosmin is an extracellular matrix protein, and genetic defects in anosmin result in human Kallmann syndrome. It functions in neural crest formation, cell adhesion, and neuronal migration. Anosmin consists of multiple domains, and it has been reported to bind heparan sulfate, FGF receptor, and UPA. In this study, we establish cell adhesion/spreading assays for anosmin and use them for antibody inhibition analyses to search for an integrin adhesion receptor. We find that α5β1, α4β1, and α9β1 integrins are needed for effective adhesive receptor function in cell adhesion and cell spreading on anosmin; adhesion is inhibited by both RGD and α4β1 CS1-based peptides...
August 9, 2016: Cell Adhesion & Migration
Yu-Chieh Chiu, Eliza L Fong, Brian J Grindel, Fred K Kasper, Daniel A Harrington, Mary C Farach-Carson
BACKGROUND: Biomaterial scaffolds that deliver growth factors such as recombinant human bone morphogenetic proteins-2 (rhBMP-2) have improved clinical bone tissue engineering by enhancing bone tissue regeneration. This approach could be further improved if the controlled delivery of bioactive rhBMP-2 were sustained throughout the duration of osteogenesis from fibrous scaffolds that provide control over dose and bioactivity of rhBMP-2. In nature, heparan sulfate attached to core proteoglycans serves as the co-receptor that delivers growth factors to support tissue morphogenesis...
December 2016: Journal of Experimental Orthopaedics
Michela Asperti, Tanja Stuemler, Maura Poli, Magdalena Gryzik, Lena Lifshitz, Esther G Meyron-Holtz, Israel Vlodavsky, Paolo Arosio
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS)...
2016: PloS One
Tadahisa Mikami, Hiroshi Kitagawa
Sulfated glycosaminoglycan (GAG) chains are a class of long linear polysaccharides that are covalently attached to multiple core proteins to form proteoglycans (PGs). PGs are major pericellular and extracellular matrix components that surround virtually all mammalian cell surfaces, and create conducive microenvironments for a number of essential cellular events, such as cell adhesion, cell proliferation, differentiation, and cell fate decisions. The multifunctional properties of PGs are mostly mediated by their respective GAG moieties, including chondroitin sulfate (CS), heparan sulfate (HS), and keratan sulfate (KS) chains...
October 6, 2016: Glycoconjugate Journal
Nirmita J Patel, Chetna Sharon, Somesh Baranwal, Rio S Boothello, Umesh R Desai, Bhaumik B Patel
Heparan sulfate (HS) plays a role in the majority of essential hallmarks of cancer, yet its ability to modulate self-renewal, especially of cancer stem cells (CSCs), remains unknown. We have discovered that a non-anticoagulant HS hexasaccharide (HS06) sequence, but not other shorter or longer sequences, selectively inhibited CSC self-renewal and induced apoptosis in colorectal, pancreatic, and breast CSCs suggesting a very general phenomenon. HS06 inhibition of CSCs relied upon early and sustained activation of p38α/β mitogen activated protein kinase (MAPK) but not other MAPKs family members i...
September 30, 2016: Oncotarget
Tabea Dierker, Chun Shao, Tatjana Haitina, Joseph Zaia, Andrea Hinas, Lena Kjellén
Proteoglycans are proteins that carry sulfated glycosaminoglycans (GAGs). They help form and maintain morphogen gradients, guiding cell migration and differentiation during animal development. While no sulfated GAGs have been found in marine sponges, chondroitin sulfate (CS) and heparan sulfate (HS) have been identified in Cnidarians, Lophotrocozoans and Ecdysozoans. The general view that nematodes such as Caenorhabditis elegans, which belong to Ecdysozoa, produce HS but only chondroitin without sulfation has therefore been puzzling...
October 5, 2016: Scientific Reports
Tarja Kunnas, Tiina Solakivi, Kirsi Määttä, Seppo T Nikkari
Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study...
October 4, 2016: Annals of Human Genetics
Benjamin Steines, David D Dickey, Jamie Bergen, Katherine J D A Excoffon, John R Weinstein, Xiaopeng Li, Ziying Yan, Mahmoud H Abou Alaiwa, Viral S Shah, Drake C Bouzek, Linda S Powers, Nicholas D Gansemer, Lynda S Ostedgaard, John F Engelhardt, David A Stoltz, Michael J Welsh, Patrick L Sinn, David V Schaffer, Joseph Zabner
The physiological components that contribute to cystic fibrosis (CF) lung disease are steadily being elucidated. Gene therapy could potentially correct these defects. CFTR-null pigs provide a relevant model to test gene therapy vectors. Using an in vivo selection strategy that amplifies successful capsids by replicating their genomes with helper adenovirus coinfection, we selected an adeno-associated virus (AAV) with tropism for pig airway epithelia. The evolved capsid, termed AAV2H22, is based on AAV2 with 5 point mutations that result in a 240-fold increased infection efficiency...
September 8, 2016: JCI Insight
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