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https://www.readbyqxmd.com/read/29142129/entry-of-human-coronavirus-nl63-to-the-cell
#1
Aleksandra Milewska, Paulina Nowak, Katarzyna Owczarek, Artur Szczepanski, Miroslaw Zarebski, Agnieszka Hoang-Bujnowicz, Krzysztof Berniak, Jacek Wojarski, Slawomir Zeglen, Zbigniew Baster, Zenon Rajfur, Krzysztof Pyrc
First steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by heparan sulfate proteoglycans, and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into LLC-Mk2 cell line and ex vivo 3D tracheobronchial tissue.Using a variety of techniques we have shown that HCoV-NL63 virions require endocytosis for successful entry to the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29125867/effects-of-cognate-non-cognate-and-synthetic-cxcr4-and-ackr3-ligands-on-human-lung-endothelial-cell-barrier-function
#2
You-Hong Cheng, Jonathan M Eby, Heather M LaPorte, Brian F Volkman, Matthias Majetschak
Recent evidence suggests that chemokine CXCL12, the cognate agonist of chemokine receptors CXCR4 and ACKR3, reduces thrombin-mediated impairment of endothelial barrier function. A detailed characterization of the effects of CXCL12 on thrombin-mediated human lung endothelial hyperpermeability is lacking and structure-function correlations are not available. Furthermore, effects of other CXCR4/ACKR3 ligands on lung endothelial barrier function are unknown. Thus, we tested the effects of a panel of CXCR4/ACKR3 ligands (CXCL12, CXCL11, ubiquitin, AMD3100, TC14012) and compared the CXCR4/ACKR3 activities of CXCL12 variants (CXCL12α/β, CXCL12(3-68), CXCL121, CXCL122, CXCL12-S-S4V, CXCL12-R47E, CXCL12-K27A/R41A/R47A) with their effects on human lung endothelial barrier function in permeability assays...
2017: PloS One
https://www.readbyqxmd.com/read/29124565/glycosaminoglycans-from-fish-swim-bladder-isolation-structural-characterization-and-bioactive-potential
#3
Yongxi Pan, Peipei Wang, Fuming Zhang, Yanlei Yu, Xing Zhang, Lei Lin, Robert J Linhardt
The swim bladder of fish is an internal gas-filled organ that allows fish to control their buoyancy and swimming depth. Fish maws (the dried swim bladders of fish) have been used over many centuries as traditional medicines, tonics and a luxurious gourmet food in China and Southeast Asia. Little is known about the structural information of polysaccharides comprising this important functional material of fish tissue. In the present study, the total glycosaminoglycan (GAG) from fish maw was characterized. Two GAGs were identified, chondroitin sulfate (CS, having a molecular weight of 18-40 kDa) and heparan sulfate (HS), corresponding to 95% and 5% of the total GAG, respectively...
November 10, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29121646/the-phosphomimetic-mutation-of-syndecan-4-binds-and-inhibits-tiam1-modulating-rac1-activity-in-pdz-interaction-dependent-manner
#4
Aniko Keller-Pinter, Bettina Ughy, Monika Domoki, Aladar Pettko-Szandtner, Tamas Letoha, Jozsef Tovari, Jozsef Timar, Laszlo Szilak
The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan...
2017: PloS One
https://www.readbyqxmd.com/read/29120519/palovarotene-inhibits-osteochondroma-formation-in-a-mouse-model-of-multiple-hereditary-exostoses
#5
Toshihiro Inubushi, Isabelle Lemire, Fumitoshi Irie, Yu Yamaguchi
Multiple hereditary exostoses (MHE), also known as multiple osteochondromas (MO), is an autosomal dominant disorder characterized by the development of multiple cartilage-capped bone tumors (osteochondromas). The large majority of patients with MHE carry loss-of-function mutations in the EXT1 or EXT2 gene, which encodes a glycosyltransferase essential for heparan sulfate (HS) biosynthesis. Increasing evidence suggests that enhanced BMP signaling resulting from loss of HS expression plays a role in osteochondroma formation in MHE...
November 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29114039/neuronal-activity-drives-fmrp-and-hspg-dependent-matrix-metalloproteinase-function-required-for-rapid-synaptogenesis
#6
Mary L Dear, Jarrod Shilts, Kendal Broadie
Matrix metalloproteinase (MMP) functions modulate synapse formation and activity-dependent plasticity. Aberrant MMP activity is implicated in fragile X syndrome (FXS), a disease caused by the loss of the RNA-binding protein FMRP and characterized by neurological dysfunction and intellectual disability. Gene expression studies in Drosophila suggest that Mmps cooperate with the heparan sulfate proteoglycan (HSPG) glypican co-receptor Dally-like protein (Dlp) to restrict trans-synaptic Wnt signaling and that synaptogenic defects in the fly model of FXS are alleviated by either inhibition of Mmp or genetic reduction of Dlp...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29113266/overexpression-of-hs6st2-is-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#7
Yi Jin, Jun He, Jing Du, Ru-Xuan Zhang, Hai-Bo Yao, Qin-Shu Shao
The purpose of the present study was to investigate the clinical significance of the expression of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in gastric cancer (GC). The Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 Array (Affymetrix; Thermo Fisher Scientific, Inc., Waltham, MA, USA) was used to identify differentially expressed genes in GC tissues vs. adjacent non-tumor gastric tissues. Candidate genes were further verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112849/astrocytes-supply-presynaptic-terminals-with-a-sweet-incentive-to-make-connections
#8
Giuseppe Condomitti, Joris de Wit
Glial cells shape neural circuits by secreting cues that contribute to the spatiotemporal control of connectivity. A new study in Neuron from Farhy-Tselnicker et al. (2017) shows that the astrocyte-secreted heparan sulfate proteoglycan GPC4 acts on presynaptic terminals to indirectly regulate AMPA receptor clustering and active synapse formation.
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29104277/heparan-sulfate-biosynthetic-system-is-inhibited-in-human-glioma-due-to-ext1-2-and-hs6st1-2-down-regulation
#9
Victor S Ushakov, Alexandra Y Tsidulko, Gabin de La Bourdonnaye, Galina M Kazanskaya, Alexander M Volkov, Roman S Kiselev, Vyacheslav V Kobozev, Diana V Kostromskaya, Alexey S Gaytan, Alexei L Krivoshapkin, Svetlana V Aidagulova, Elvira V Grigorieva
Heparan sulfate (HS) is an important component of the extracellular matrix and cell surface, which plays a key role in cell-cell and cell-matrix interactions. Functional activity of HS directly depends on its structure, which determined by a complex system of HS biosynthetic enzymes. During malignant transformation, the system can undergo significant changes, but for glioma, HS biosynthesis has not been studied in detail. In this study, we performed a comparative analysis of the HS biosynthetic system in human gliomas of different grades...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29100299/coupling-to-a-cancer-selective-heparan-sulfate-targeted-branched-peptide-can-by-pass-breast-cancer-cell-resistance-to-methotrexate
#10
Lorenzo Depau, Jlenia Brunetti, Chiara Falciani, Silvia Scali, Giulia Riolo, Elisabetta Mandarini, Alessandro Pini, Luisa Bracci
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097791/heparanase-and-macrophage-interplay-in-the-onset-of-liver-fibrosis
#11
Maria Francesca Secchi, Marika Crescenzi, Valentina Masola, Francesco Paolo Russo, Annarosa Floreani, Maurizio Onisto
The heparan sulfate endoglycosidase heparanase (HPSE) is involved in tumor growth, chronic inflammation and fibrosis. Since a role for HPSE in chronic liver disease has not been demonstrated to date, the current study was aimed at investigating the involvement of HPSE in the pathogenesis of chronic liver injury. Herein, we revealed that HPSE expression increased in mouse livers after carbon tetrachloride (CCl4)-mediated chronic induction of fibrosis, but with a trend to decline during progression of the disease...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29093715/rantes-ccl5-induces-collagen-degradation-by-activating-mmp-1-and-mmp-13-expression-in-human-rheumatoid-arthritis-synovial-fibroblasts
#12
Solomon A Agere, Nahid Akhtar, Jeffery M Watson, Salahuddin Ahmed
Regulated on activation, normal T expressed, and secreted (RANTES)/CC ligand 5 (CCL5) participates in rheumatoid arthritis (RA) pathogenesis by facilitating leukocyte infiltration, however, its other pathological functions are not fully defined in RA. In the present study, we evaluated the effect of RANTES/CCL5 on tissue degrading enzymes matrix metalloproteinase-1 (MMP-1) and MMP-13 expression and its contribution to the progressive joint damage by RA synovial fibroblasts (RASFs). Our results showed that RANTES/CCL5 dose dependently induced MMP-1 and MMP-13 expression in monolayers and three-dimensional (3D) micromass of human RASFs, which correlated with an increase in collagenase activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29089873/exploiting-heparan-sulfate-proteoglycans-in-human-neurogenesis-controlling-lineage-specification-and-fate
#13
REVIEW
Chieh Yu, Lyn R Griffiths, Larisa M Haupt
Unspecialized, self-renewing stem cells have extraordinary application to regenerative medicine due to their multilineage differentiation potential. Stem cell therapies through replenishing damaged or lost cells in the injured area is an attractive treatment of brain trauma and neurodegenerative neurological disorders. Several stem cell types have neurogenic potential including neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). Currently, effective use of these cells is limited by our lack of understanding and ability to direct lineage commitment and differentiation of neural lineages...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29089598/cellular-uptake-of-modified-aminoglycosides
#14
Kaivin Hadidi, Ezequiel Wexselblatt, Jeffrey D Esko, Yitzhak Tor
The uptake of modified amino- and guanidino-glycosides derived from kanamycin, tobramycin and neomycin in native and mutant CHO cells is examined using confocal microscopy and flow cytometry, illustrating the significance of multivalency for mammalian cell internalization of carriers that specifically interact with cell surface heparan sulfate proteoglycans.The Journal of Antibiotics advance online publication, 1 November 2017; doi:10.1038/ja.2017.131.
November 1, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/29081732/lar-rptp-clustering-is-modulated-by-competitive-binding-between-synaptic-adhesion-partners-and-heparan-sulfate
#15
Seoung Youn Won, Cha Yeon Kim, Doyoun Kim, Jaewon Ko, Ji Won Um, Sung Bae Lee, Matthias Buck, Eunjoon Kim, Won Do Heo, Jie-Oh Lee, Ho Min Kim
The leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that direct axonal growth and neuronal regeneration. LAR-RPTPs are also synaptic adhesion molecules that form trans-synaptic adhesion complexes by binding to various postsynaptic adhesion ligands, such as Slit- and Trk-like family of proteins (Slitrks), IL-1 receptor accessory protein-like 1 (IL1RAPL1), interleukin-1 receptor accessory protein (IL-1RAcP) and neurotrophin receptor tyrosine kinase C (TrkC), to regulate synaptogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29081389/toxoplasma-gondii-ron4-binds-to-heparan-sulfate-on-the-host-cell-surface
#16
Hitoshi Takemae, Kyousuke Kobayashi, Tatsuki Sugi, Yongmei Han, Haiyan Gong, Akiko Ishiwa, Frances C Recuenco, Fumi Murakoshi, Ryo Takano, Yuho Murata, Kisaburo Nagamune, Taisuke Horimoto, Hiroomi Akashi, Kentaro Kato
Toxoplasma gondii rhoptry neck protein 4 (TgRON4) is a component of the moving junction, a key structure for host cell invasion. We previously showed that host cellular β-tubulin is a binding partner of TgRON4 in the invasion process. Here, to identify other binding partners of TgRON4 in the host cell, we examined the binding of TgRON4 to components of the host cell surface. TgRON4 binds to various mammalian cells, but this binding disappeared in glycosaminoglycan- and heparan sulfate-deficient CHO cells and after heparitinase treatment of mammalian cells...
October 25, 2017: Parasitology International
https://www.readbyqxmd.com/read/29070611/solution-structure-of-cxcl13-and-heparan-sulfate-binding-show-that-gag-binding-site-and-cellular-signalling-rely-on-distinct-domains
#17
Yoan R Monneau, Lingjie Luo, Nehru Viji Sankaranarayanan, Balaji Nagarajan, Romain R Vivès, Françoise Baleux, Umesh R Desai, Fernando Arenzana-Seidedos, Hugues Lortat-Jacob
Chemokines promote directional cell migration through binding to G-protein-coupled receptors, and as such are involved in a large array of developmental, homeostatic and pathological processes. They also interact with heparan sulfate (HS), the functional consequences of which depend on the respective location of the receptor- and the HS-binding sites, a detail that remains elusive for most chemokines. Here, to set up a biochemical framework to investigate how HS can regulate CXCL13 activity, we solved the solution structure of CXCL13...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29069492/lectin-zg16p-inhibits-proliferation-of-human-colorectal-cancer-cells-via-its-carbohydrate-binding-sites
#18
Akiko Mito, Yukiko Nakano, Takako Saitoh, Sabine S S Gouraud, Yoshiki Yamaguchi, Toshiro Sato, Nobuo Sasaki, Kyoko Kojima-Aikawa
Zymogen granule protein 16 (ZG16p) is a soluble lectin that binds to both mannose and heparin/heparan sulfate. It is highly expressed in the human digestive tract and is secreted into the mucus. In this study, we investigated the effect of ZG16p on the proliferation of human colorectal cancer cells. Overexpression of ZG16p in Caco-2 cells decreased cell growth. Recombinant ZG16p markedly inhibited proliferation of Caco-2, LS174T, HCT116 and HCT15 cells. Caco-2 cell growth was not inhibited by two mutated ZG16p proteins, D151A and M5 (K36A, R37A, R53A, R55A and R79A) lacking mannose- and heparin-binding activities, respectively...
October 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/29069438/loss-of-heparan-sulfate-in-the-niche-leads-to-tumor-like-germ-cell-growth-in-the-drosophila-testis
#19
Daniel C Levings, Hiroshi Nakato
The stem cell niche normally prevents aberrant stem cell behaviors that lead to cancer formation. Recent studies suggest that some cancers are derived from endogenous populations of adult stem cells that have somehow escaped from normal control by the niche. However, the molecular mechanisms by which the niche retains stem cells locally and tightly controls their divisions are poorly understood. Here, we demonstrate that the presence of heparan sulfate (HS), a class glygosaminoglycan chains, in the Drosophila germline stem cell niche prevents tumor formation in the testis...
October 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/29068543/covalent-incorporation-of-heparin-improves-chondrogenesis-in-photocurable-gelatin-methacryloyl-hydrogels
#20
Gabriella C J Brown, Khoon S Lim, Brooke L Farrugia, Gary J Hooper, Tim B F Woodfield
Multicomponent gelatin-methacryloyl (GelMA) hydrogels are regularly adopted for cartilage tissue engineering (TE) applications, where optimizing chemical modifications for preserving biofunctionality is often overlooked. This study investigates the biological effect of two different modification methods, methacrylation and thiolation, to copolymerize GelMA and heparin. The native bioactivity of methacrylated heparin (HepMA) and thiolated heparin (HepSH) is evaluated via thromboplastin time and heparan sulfate-deficient myeloid cell-line proliferation assay, demonstrating that thiolation is superior for preserving anticoagulation and growth factor signaling capacity...
October 25, 2017: Macromolecular Bioscience
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