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Heparan sulfate

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https://www.readbyqxmd.com/read/28943240/control-of-cell-shape-neurite-outgrowth-and-migration-by-a-nogo-a-hspg-interaction
#1
Anissa Kempf, Enrica Boda, Jessica C F Kwok, Rafael Fritz, Valentina Grande, Andrea M Kaelin, Zorica Ristic, Andre Schmandke, Antonio Schmandke, Bjoern Tews, James W Fawcett, Olivier Pertz, Annalisa Buffo, Martin E Schwab
Heparan sulfate proteoglycans (HSPGs) critically modulate adhesion-, growth-, and migration-related processes. Here, we show that the transmembrane protein, Nogo-A, inhibits neurite outgrowth and cell spreading in neurons and Nogo-A-responsive cell lines via HSPGs. The extracellular, active 180 amino acid Nogo-A region, named Nogo-A-Δ20, binds to heparin and brain-derived heparan sulfate glycosaminoglycans (GAGs) but not to the closely related chondroitin sulfate GAGs. HSPGs are required for Nogo-A-Δ20-induced inhibition of adhesion, cell spreading, and neurite outgrowth, as well as for RhoA activation...
September 18, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28941021/immobilization-of-vitronectin-binding-heparan-sulfates-onto-surfaces-to-support-human-pluripotent-stem-cells
#2
Lynn Yap, Sadasivam Murali, Gajadhar Bhakta, Drew M Titmarsh, Allen Kuan-Liang Chen, Lyn Chiin Sim, Muriel Bardor, Yu Ming Lim, James C H Goh, Steve K W Oh, Andre B H Choo, Andre J van Wijnen, David E Robinson, Jason D Whittle, William R Birch, Robert D Short, Victor Nurcombe, Simon M Cool
Functionalizing medical devices with polypeptides to enhance their performance has become important for improved clinical success. The extracellular matrix (ECM) adhesion protein vitronectin (VN) is an effective coating, although the chemistry used to attach VN often reduces its bioactivity. In vivo, VN binds the ECM in a sequence-dependent manner with heparan sulfate (HS) glycosaminoglycans. We reasoned therefore that sequence-based affinity chromatography could be used to isolate a VN-binding HS fraction (HS9) for use as a coating material to capture VN onto implant surfaces...
September 20, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28940845/emerging-roles-of-syndecan-2-in-epithelial-and-mesenchymal-cancer-progression
#3
REVIEW
Maria Mytilinaiou, Dragana Nikitovic, Aikaterini Berdiaki, Antonis Kostouras, Antonis Papoutsidakis, Aristidis M Tsatsakis, George N Tzanakakis
Syndecan 2 (SDC2) belongs to a four-member family of evolutionary conserved small type I transmembrane proteoglycans consisting of a protein core to which glycosaminoglycan chains are covalently attached. SDC2 is a cell surface heparan sulfate proteoglycan, which is increasingly drawing attention for its distinct characteristics and its participation in numerous cell functions, including those related to carcinogenesis. Increasing evidence suggests that the role of SDC2 in cancer pathogenesis is dependent on cancer tissue origin rendering its use as a biomarker/therapeutic target feasible...
September 23, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28938567/gemcitabine-induced-heparanase-promotes-aggressiveness-of-pancreatic-cancer-cells-via-activating-egfr-signaling
#4
Jin-Wen Song, Ying-Xia Tan, Su-Bo Li, Shi-Kun Zhang, Lu-Ming Wan, Shou-Ping Ji, Hong Zhou, Zhi-Hang Zhou, Feng Gong
Pancreatic cancer (PC), characterized by aggressive local invasion and metastasis, is one of the most malignant cancers. Gemcitabine is currently used as the standard drug for the treatment of advanced and metastatic PC, but with limited efficacy. In this study, we demonstrated that gemcitabine increased the expression of heparanase (HPA1), the only known mammalian endoglycosidase capable of cleaving heparan sulfate, both in vitro and in vivo. Furthermore, overexpression of HPA1 in PC cell lines enhanced proliferation and invasion, accompanied with elevated phosphorylation of EGFR...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28933686/heparan-sulfate-as-a-receptor-for-poxvirus-infections-and-as-a-target-for-antiviral-agents
#5
Mayank Khanna, Charani Ranasinghe, Ronald Jackson, Christopher Richard Parish
To establish the importance of virus-heparan sulfate (HS) interactions in virus infectivity, the poxvirus vaccinia virus (VACV) was used, as it binds HS and has both enveloped virus (EV) and non-enveloped mature virus (MV) forms. Initial studies showed that heparin inhibited plaque formation by both MV-rich WR and EV-rich IHD-J strains of VACV, with the EV-rich strain also losing trademark 'comet'-shaped plaques. However, using GFP-tagged EV and MV forms of VACV, based on IC50 values, heparin was 16-fold more effective at inhibiting the infectivity of the EV form compared to the MV form...
September 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28928087/complement-factor-h-in-amd-bridging-genetic-associations-and-pathobiology
#6
REVIEW
Christopher B Toomey, Lincoln V Johnson, Catherine Bowes Rickman
AMD is a complex multifactorial disease characterized in its early stages by lipoprotein accumulations in BrM, seen on fundoscopic exam as drusen, and in its late forms by neovascularization ("wet") or geographic atrophy of the RPE cell layer ("dry"). Genetic studies have strongly supported a relationship between the alternative complement cascade, in particular the common H402 variant in Complement Factor H (CFH) and development of AMD. However, the functional significance of the CFH Y402H polymorphism remains elusive...
September 16, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28927006/emerging-roles-of-heparanase-in-viral-pathogenesis
#7
REVIEW
Neel Thakkar, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla
Heparan sulfate (HS) is ubiquitously expressed on mammalian cells. It is a polysaccharide that binds growth factors, cytokines, and chemokines, and thereby controls several important physiological functions. Ironically, many human pathogens including viruses interact with it for adherence to host cells. HS functions can be regulated by selective modifications and/or selective cleavage of the sugar chains from the cell surface. In mammals, heparanase (HPSE) is the only known enzyme capable of regulating HS functions via a selective endoglycosidase activity that cleaves polymeric HS chains at internal sites...
September 18, 2017: Pathogens
https://www.readbyqxmd.com/read/28921412/how-close-are-we-to-therapies-for-sanfilippo-disease
#8
REVIEW
Lidia Gaffke, Karolina Pierzynowska, Ewa Piotrowska, Grzegorz Węgrzyn
Sanfilippo disease is one of mucopolysaccharidoses (MPS), a group of lysosomal storage diseases characterized by accumulation of partially degraded glycosaminoglycans (GAGs). It is classified as MPS type III, though it is caused by four different genetic defects, determining subtypes A, B, C and D. In each subtype of MPS III, the primary storage GAG is heparan sulfate (HS), but mutations leading to A, B, C, and D subtypes are located in genes coding for heparan N-sulfatase (the SGSH gene), α-N-acetylglucosaminidase (the NAGLU gene), acetyl-CoA:α-glucosaminide acetyltransferase (the HGSNAT gene), and N-acetylglucosamine-6-sulfatase (the GNS gene), respectively...
September 18, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28918020/rationally-engineered-aav-capsids-improve-transduction-and-volumetric-spread-in-the-cns
#9
Nicholas M Kanaan, Rhyomi C Sellnow, Sanford L Boye, Ben Coberly, Antonette Bennett, Mavis Agbandje-McKenna, Caryl E Sortwell, William W Hauswirth, Shannon E Boye, Fredric P Manfredsson
Adeno-associated virus (AAV) is the most common vector for clinical gene therapy of the CNS. This popularity originates from a high safety record and the longevity of transgene expression in neurons. Nevertheless, clinical efficacy for CNS indications is lacking, and one reason for this is the relatively limited spread and transduction efficacy in large regions of the human brain. Using rationally designed modifications of the capsid, novel AAV capsids have been generated that improve intracellular processing and result in increased transgene expression...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#10
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 13, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28910175/neurotrophic-keratopathy-therapeutic-approach-using-a-novel-matrix-regenerating-agent
#11
Marta Guerra, Sara Marques, João Quadrado Gil, Joana Campos, Paula Ramos, Andreia Martins Rosa, Maria João Quadrado, Joaquim Neto Murta
PURPOSE: To evaluate the efficacy and tolerance of a new matrix-regenerating agent (RGTA), Cacicol(®), a polymer that mimics heparan sulfates bound to extracellular matrix proteins, avoiding its proteolysis, to treat neurotrophic keratopathy (NK). METHODS: Uncontrolled prospective clinical study performed between January 2014 and May 2016. Twenty-five patients (25 eyes) with corneal neurotrophic ulcers, nonresponsive to at least 2 weeks of conservative therapy, were treated with Cacicol, instilled once/twice a week...
September 14, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28895925/bovine-lactoferrin-inhibits-dengue-virus-infectivity-by-interacting-with-heparan-sulfate-low-density-lipoprotein-receptor-and-dc-sign
#12
Jo-Mei Chen, Yi-Chin Fan, Jen-Wei Lin, Yi-Ying Chen, Wei-Li Hsu, Shyan-Song Chiou
Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue virus (DENV) infection. In this study, we evaluated the antiviral effect of bLF against DENV infection in vivo and in vitro. Bovine LF significantly inhibited the infection of the four serotypes of DENV in Vero cells. In the time-of-drug addition test, DENV-2 infection was remarkably inhibited when bLF was added during or prior to the occurrence of virus attachment...
September 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28895470/generation-of-a-close-to-native-in-vitro-system-to-study-lung-cells-ecm-crosstalk
#13
Zuzana Garlikova, Ana Catarina Silva, Ana Rabata, David Potesil, Ivana Ihnatova, Jana Dumkova, Zuzana Koledova, Zbynek Zdrahal, Vladimir Vinarsky, Ales Hample, Perpetua Pinto-do-O, Diana S Nascimento
Extracellular matrix (ECM) is an essential component of the tissue microenvironment, actively shaping cellular behavior. In vitro culture systems are often poor in ECM constituents thus not allowing for naturally occurring cell-ECM interactions. This study reports on a straightforward and efficient method for generation of ECM scaffolds from lung tissue and its subsequent in vitro application using primary lung cells. Mouse lung tissue was subjected to decellularization with 0.2% sodium dodecyl sulfate, hypotonic solutions and DNase...
September 12, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28894089/heparan-sulfate-proteoglycans-present-pcsk9-to-the-ldl-receptor
#14
Camilla Gustafsen, Ditte Olsen, Joachim Vilstrup, Signe Lund, Anika Reinhardt, Niels Wellner, Torben Larsen, Christian B F Andersen, Kathrin Weyer, Jin-Ping Li, Peter H Seeberger, Søren Thirup, Peder Madsen, Simon Glerup
Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28893538/indispensable-role-of-lipoprotein-bound-apoe-in-adipogenesis-and-endocytosis-induced-by-postprandial-trl
#15
Mingyu Zhang, Yanhong Li, Xuehong Wei, Feng Tian, Fan Ouyang, Shuiping Zhao, Ling Liu
Diet-associated obesity is coexisted with postprandial hypertriglyceridemia that indicates increased number of triglyceride-rich lipoproteins (TRL). This study aimed to investigate the effect of postprandial TRL-bound apolipoprotein E (ApoE) on adipogenesis and potential mechanisms. 3T3-L1 cells were cultured with (i) human TRL (h-TRL) with or without insulin, or (ii) TRL from wild type mice (WT-TRL) or ApoE knock-out mice (EKO-TRL) and insulin. The differentiating adipocytes were incubated with different kinds of TRL labeled by red fluorescence and confocal microscopy was performed...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28893506/cytochrome-b561-copper-%C3%AE-cleaved-amyloid-precursor-protein-and-niemann-pick-c1-protein-are-involved-in-ascorbate-induced-release-and-membrane-penetration-of-heparan-sulfate-from-endosomal-s-nitrosylated-glypican-1
#16
Fang Cheng, Lars-Åke Fransson, Katrin Mani
Ascorbate-induced release of heparan sulfate from S-nitrosylated heparan sulfate proteoglycan glypican-1 takes place in endosomes. Heparan sulfate penetrates the membrane and is transported to the nucleus. This process is dependent on copper and on expression and processing of the amyloid precursor protein. It remains unclear how exogenously supplied ascorbate can generate HS-anMan in endosomes and how passage through the membrane is facilitated. Here we have examined wild-type, Alzheimer Tg2576 and amyloid precursor protein (-/-) mouse fibroblasts and human fetal and Niemann-Pick C1 fibroblasts by using deconvolution immunofluorescence microscopy, siRNA technology and [S(35)]sulfate-labeling, vesicle isolation and gel chromatography...
September 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28893348/overexpression-of-glypican-5-gpc5-inhibits-prostate-cancer-cell-proliferation-and-invasion-via-suppressing-sp1-mediated-emt-and-activation-of-wnt-%C3%AE-catenin-signaling
#17
Yu Sun, Kai Xu, Miao He, Guilian Fan, Hongming Lu
Glypican 5 (GPC5) belongs to the family of heparan sulfate proteoglycans (HSPGs). It was initially known as a regulatorof growth factors and morphogens. Recently, there have been reports on its correlation with the tumorigenic process in the development of some cancers. However, little is known about its precise role in prostate cancer (PCa). In the present study, we explored the expression pattern and biological functions of GPC5 in PCa cells. Our results showed that GPC5 was lowly expressed in PCa cell lines...
September 6, 2017: Oncology Research
https://www.readbyqxmd.com/read/28888912/chemotherapy-induces-secretion-of-exosomes-loaded-with-heparanase-that-degrades-extracellular-matrix-and-impacts-tumor-and-host-cell-behavior
#18
Shyam K Bandari, Anurag Purushothaman, Vishnu C Ramani, Garrett J Brinkley, Darshan S Chandrashekar, Sooryanarayana Varambally, James A Mobley, Yi Zhang, Elizabeth E Brown, Israel Vlodavsky, Ralph D Sanderson
The heparan sulfate-degrading enzyme heparanase promotes the progression of many cancers by driving tumor cell proliferation, metastasis and angiogenesis. Heparanase accomplishes this via multiple mechanisms including its recently described effect on enhancing biogenesis of tumor exosomes. Because we recently discovered that heparanase expression is upregulated in myeloma cells that survive chemotherapy, we were prompted to investigate the impact of anti-myeloma drugs on exosome biogenesis. When myeloma cells were exposed to the commonly utilized anti-myeloma drugs bortezomib, carfilzomib or melphalan, exosome secretion by the cells was dramatically enhanced...
September 6, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28888201/tgf-%C3%AE-1-presenting-enzymatically-cross-linked-injectable-hydrogels-for-improved-chondrogenesis
#19
Aditya Arora, Aman Mahajan, Dhirendra S Katti
In this work, we developed a novel enzymatically cross-linked injectable hydrogel composed of carboxymethyl cellulose (CMC), sulfated carboxymethyl cellulose (sCMC) and gelatin for delivery of infrapatellar fat pad derived MSCs and articular chondrocytes to a cartilage defect site while enabling TGF-β1 mediated chondrogenesis. The sCMC component in the hydrogel served the purpose of mimicking heparan sulfate and thus enabled strong binding with TGF-β1 and its consequential long term presentation to the encapsulated cells...
August 24, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28874572/dendritic-space-filling-requires-a-neuronal-type-specific-extracellular-permissive-signal-in-drosophila
#20
Amy R Poe, Lingfeng Tang, Bei Wang, Yun Li, Maria L Sapar, Chun Han
Neurons sometimes completely fill available space in their receptive fields with evenly spaced dendrites to uniformly sample sensory or synaptic information. The mechanisms that enable neurons to sense and innervate all space in their target tissues are poorly understood. Using Drosophila somatosensory neurons as a model, we show that heparan sulfate proteoglycans (HSPGs) Dally and Syndecan on the surface of epidermal cells act as local permissive signals for the dendritic growth and maintenance of space-filling nociceptive C4da neurons, allowing them to innervate the entire skin...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
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