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Heparan sulfate

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https://www.readbyqxmd.com/read/29332576/current-understanding-of-physicochemical-mechanisms-for-cell-membrane-penetration-of-arginine-rich-cell-penetrating-peptides-role-of-glycosaminoglycan-interactions
#1
Yuki Takechi-Haraya, Hiroyuki Saito
Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet...
January 11, 2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29330473/endothelial-heparan-sulfate-deficiency-reduces-inflammation-and-fibrosis-in-murine-diabetic-nephropathy
#2
Ditmer T Talsma, Kirankumar Katta, Marieke A B Ettema, Berna Kel, Marion Kusche-Gullberg, Moh R Daha, Coen A Stegeman, Jacob van den Born, Lianchun Wang
Inflammation plays a vital role in the development of diabetic nephropathy, but the underlying regulatory mechanisms are only partially understood. Our previous studies demonstrated that, during acute inflammation, endothelial heparan sulfate (HS) contributes to the adhesion and transendothelial migration of leukocytes into perivascular tissues by direct interaction with L-selectin and the presentation of bound chemokines. In the current study, we aimed to assess the role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic nephropathy mouse model...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29322326/heparan-sulfate-accumulation-and-perlecan-hspg2-up-regulation-in-tumour-tissue-predict-low-relapse-free-survival-for-patients-with-glioblastoma
#3
Galina M Kazanskaya, Alexandra Y Tsidulko, Alexander M Volkov, Roman S Kiselev, Anastasia V Suhovskih, Vyacheslav V Kobozev, Alexei S Gaytan, Svetlana V Aidagulova, Alexei L Krivoshapkin, Elvira V Grigorieva
Glycosaminoglycans are major components of brain extracellular matrix (ECM), although heparan sulfate (HS) contribution in brain physiology and carcinogenesis remains underinvestigated. This study examined HS content and distribution in glioblastoma multiforme (GBM) tissues in the context of potential molecular mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue samples and paraffin-embedded tissues for 31 patients with different prognosis were investigated. HS expression was demonstrated in 50-55% of the GBM tumours by immunohistochemistry (IHC), while almost no HS content was detected in the surrounding paratumourous brain tissues...
January 10, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29316553/oocyte-cytoplasmic-gas6-and-heparan-sulfate-hs-are-required-to-establish-the-open-chromatin-state-in-nuclei-during-remodeling-and-reprogramming
#4
Kyeoung-Hwa Kim, Eun-Young Kim, Su-Yeon Lee, Jung-Jae Ko, Kyung-Ah Lee
BACKGROUND/AIMS: Previously, we found that silencing of growth arrest-specific gene 6 (Gas6) in oocytes impaired cytoplasmic maturation, resulting in failure of sperm chromatin decondensation (SCD) and pronuclear (PN) formation after fertilization. Thus, we conducted this study to determine the effect of Gas6 RNAi on downstream genes and to elucidate the working mechanism of Gas6 on oocyte cytoplasmic maturation and SCD. METHODS: Using RT-PCR, Western blot and immunofluorescence, the expression levels of various target genes and the localization of heparan sulfate (HS) were analyzed after Gas6 RNAi...
December 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29315274/synthesized-heparan-sulfate-competitors-attenuate-pseudomonas-aeruginosa-lung-infection
#5
Nicola Ivan Lorè, Noemi Veraldi, Camilla Riva, Barbara Sipione, Lorenza Spagnuolo, Ida De Fino, Medede Melessike, Elisa Calzi, Alessandra Bragonzi, Annamaria Naggi, Cristina Cigana
Several chronic respiratory diseases are characterized by recurrent and/or persistent infections, chronic inflammatory responses and tissue remodeling, including increased levels of glycosaminoglycans which are known structural components of the airways. Among glycosaminoglycans, heparan sulfate (HS) has been suggested to contribute to excessive inflammatory responses. Here, we aim at (i) investigating whether long-term infection by Pseudomonas aeruginosa, one of the most worrisome threat in chronic respiratory diseases, may impact HS levels, and (ii) exploring HS competitors as potential anti-inflammatory drugs during P...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29310785/isolation-and-functional-analysis-of-syndecans
#6
Pyong Woo Park
Syndecans comprise a major family of cell surface heparan sulfate proteoglycans (HSPGs). Syndecans are composed of sulfated glycosaminoglycans (GAGs), heparan sulfate (HS) or both HS and chondroitin sulfate (CS), attached covalently to core proteins. Syndecans regulate many cellular processes, such as adhesion, proliferation, and migration. Syndecans bind and regulate molecules primarily through their HS chains, but do not bind to all HS/heparin-binding molecules. Furthermore, mice ablated for the syndecan-1 or -4 gene do not show major developmental abnormalities, but they do show striking pathological phenotypes when challenged with infectious or inflammatory stimuli and conditions, suggesting that certain functions of syndecans are specific and cannot be compensated for by other syndecans or other HSPGs...
2018: Methods in Cell Biology
https://www.readbyqxmd.com/read/29305908/exostosin-like-2-regulates-fgf2-signaling-by-controlling-the-endocytosis-of-fgf2
#7
Satomi Nadanaka, Hiroshi Kitagawa
BACKGROUND: Heparan sulfate proteoglycans are ubiquitously expressed on cell surfaces and in extracellular matrices, and are engaged in heparin-binding growth factor-related signal transduction. Thus, changes in the amounts, structures, and chain lengths of heparan sulfate have profound effects on aspects of cell growth controlled by heparin-binding growth factors such as FGF2. Exostosin glycosyltransferases (EXT1, EXT2, EXTL1, EXTL2, and EXTL3) control heparan sulfate biosynthesis, and the expression levels of their genes regulate the amounts, chain lengths, and sulfation patterns of heparan sulfate...
January 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29305777/glycosaminoglycans-from-bovine-eye-vitreous-humour-and-interaction-with-collagen-type-ii
#8
Yanfei Peng, Yanlei Yu, Lei Lin, Xinyue Liu, Xing Zhang, Peipei Wang, Pauline Hoffman, So Young Kim, Fuming Zhang, Robert J Linhardt
Glycosaminoglycans (GAGs) play an important role in stabilizing the gel state of eye vitreous humour. In this study, the composition of GAGs present in bovine eye vitreous was characterized through disaccharide analysis by liquid chromatography-mass spectrometry. The interaction of GAGs with collagen type II was assessed using surface plasmon resonance (SPR). The percentage of hyaluronic acid (HA), chondroitin sulfate (CS) and heparan sulfate (HS), of total GAG, were 96.2%, 3.5% and 0.3%, respectively. The disaccharide composition of CS consisted of 4S (49%), 0S (38%) 6S (12%), 2S6S (1...
January 5, 2018: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29290153/the-role-of-heparan-sulfate-in-inflammation-and-the-development-of-biomimetics-as-anti-inflammatory-strategies
#9
Brooke L Farrugia, Megan S Lord, James Melrose, John M Whitelock
Key events that occur during inflammation include the recruitment, adhesion, and transmigration of leukocytes from the circulation to the site of inflammation. These events are modulated by chemokines, integrins, and selectins and the interaction of these molecules with glycosaminoglycans, predominantly heparan sulfate (HS). The development of HS/heparin mimetics that interfere or inhibit the interactions that occur between glycosaminoglycans and modulators of inflammation holds great potential for use as anti-inflammatory therapeutics...
November 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29290138/heparan-sulfate-proteoglycans-as-relays-of-neuroinflammation
#10
Paul O'Callaghan, Xiao Zhang, Jin-Ping Li
Heparan sulfate proteoglycans (HSPGs) are implicated as inflammatory mediators in a variety of settings, including chemokine activation, which is required to recruit circulating leukocytes to infection sites. Heparan sulfate (HS) polysaccharide chains are highly interactive and serve co-receptor roles in multiple ligand:receptor interactions. HS may also serve as a storage depot, sequestering ligands such as cytokines and restricting their access to binding partners. Heparanase, through its ability to fragment HS chains, is a key regulator of HS function and has featured prominently in studies of HS's involvement in inflammatory processes...
November 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29288051/acceleration-of-amyloid-fibril-formation-by-carboxyl-terminal-truncation-of-human-serum-amyloid-a
#11
Masafumi Tanaka, Toru Kawakami, Nozomi Okino, Kaoru Sasaki, Kiwako Nakanishi, Hiroka Takase, Toshiyuki Yamada, Takahiro Mukai
Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis. Although the full-length SAA is 104 amino acids long, the C-terminal-truncated SAA lacking mainly residues 77-104 is predominantly deposited in AA amyloidosis. Nevertheless, the amyloid fibril formation of such truncated forms of human SAA has never been investigated. In the present study, we examined the effect of C-terminal truncation on amyloid fibril formation of human SAA induced by heparan sulfate (HS). Circular dichroism (CD) measurements demonstrated that the C-terminal truncation induces a reduced α-helical structure of the SAA molecule...
December 26, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29277722/the-pathogenic-roles-of-heparan-sulfate-deficiency-in-hereditary-multiple-exostoses
#12
REVIEW
Maurizio Pacifici
Heparan sulfate (HS) is an essential component of cell surface and matrix proteoglycans (HS-PGs) that include syndecans and perlecan. Because of their unique structural features, the HS chains are able to specifically interact with signaling proteins -including bone morphogenetic proteins (BMPs)- via their HS-binding domain, regulating protein availability, distribution and action on target cells. Hereditary Multiple Exostoses (HME) is a rare pediatric disorder linked to germline heterozygous loss-of-function mutations in EXT1 or EXT2 that encode Golgi-resident glycosyltransferases responsible for HS synthesis, resulting in a systemic HS deficiency...
December 22, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29277006/hiv-internalization-into-oral-and-genital-epithelial-cells-by-endocytosis-and-macropinocytosis-leads-to-viral-sequestration-in-the-vesicles
#13
Aizezi Yasen, Rossana Herrera, Kristina Rosbe, Kathy Lien, Sharof M Tugizov
Recently, we showed that HIV-1 is sequestered, i.e., trapped, in the intracellular vesicles of oral and genital epithelial cells. Here, we investigated the mechanisms of HIV-1 sequestration in vesicles of polarized tonsil, foreskin and cervical epithelial cells. HIV-1 internalization into epithelial cells is initiated by multiple entry pathways, including clathrin-, caveolin/lipid raft-associated endocytosis and macropinocytosis. Inhibition of HIV-1 attachment to galactosylceramide and heparan sulfate proteoglycans, and virus endocytosis and macropinocytosis reduced HIV-1 sequestration by 30-40%...
December 22, 2017: Virology
https://www.readbyqxmd.com/read/29258589/a-comparative-study-of-chondroitin-sulfate-and-heparan-sulfate-for-directing-three-dimensional-chondrogenesis-of-mesenchymal-stem-cells
#14
Tianyi Wang, Fan Yang
BACKGROUND: Mesenchymal stem cells (MSCs) hold great promise for cartilage repair given their relative abundance, ease of isolation, and chondrogenic potential. To enhance MSC chondrogenesis, extracellular matrix components can be incorporated into three-dimensional (3D) scaffolds as an artificial cell niche. Chondroitin sulfate (CS)-containing hydrogels have been shown to support 3D chondrogenesis, but the effects of varying CS concentration and hydrogel stiffness on 3D MSC chondrogenesis remains elusive...
December 19, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29251725/broad-spectrum-non-toxic-antiviral-nanoparticles-with-a-virucidal-inhibition-mechanism
#15
Valeria Cagno, Patrizia Andreozzi, Marco D'Alicarnasso, Paulo Jacob Silva, Marie Mueller, Marie Galloux, Ronan Le Goffic, Samuel T Jones, Marta Vallino, Jan Hodek, Jan Weber, Soumyo Sen, Emma-Rose Janeček, Ahmet Bekdemir, Barbara Sanavio, Chiara Martinelli, Manuela Donalisio, Marie-Anne Rameix Welti, Jean-Francois Eleouet, Yanxiao Han, Laurent Kaiser, Lela Vukovic, Caroline Tapparel, Petr Král, Silke Krol, David Lembo, Francesco Stellacci
Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them...
December 18, 2017: Nature Materials
https://www.readbyqxmd.com/read/29244851/inhibition-of-merozoite-invasion-and-transient-de-sequestration-by-sevuparin-in-humans-with-plasmodium-falciparum-malaria
#16
Anna M Leitgeb, Prakaykaew Charunwatthana, Ronnatrai Rueangveerayut, Chirapong Uthaisin, Kamolrat Silamut, Kesinee Chotivanich, Patima Sila, Kirsten Moll, Sue J Lee, Maria Lindgren, Erik Holmer, Anna Färnert, Mpungu S Kiwuwa, Jens Kristensen, Christina Herder, Joel Tarning, Mats Wahlgren, Arjen M Dondorp
SEVERE MALARIA: Even with the best available treatment, the mortality from severe Plasmodium falciparum malaria remains high. Typical features at death are high parasite loads and obstructed micro- vasculature. Infected erythrocytes (IE) containing mature parasites bind to the host receptor heparan sulfate, which is also an important receptor for merozoite invasion. To block merozoite invasion has not previously been proposed as an adjunctive therapeutic approach but it may preclude the early expansion of an infection that else leads to exacerbated sequestration and death...
2017: PloS One
https://www.readbyqxmd.com/read/29242821/regulation-of-regeneration-by-heparan-sulfate-proteoglycans-in-the-extracellular-matrix
#17
David M Gardiner
Just as the building of a house requires a blueprint, the rebuilding of lost or damaged body parts through regeneration requires a set of instructions for the assembly of the various tissues into the right places. Much progress has been made in understanding how to control the differentiation of different cell types to provide the building blocks for regeneration, such as bone, muscle, blood vessels and nerves/Schwann cells. These are the cells that follow the blueprint (the pattern-following cells) and end up in the right places relative to each other in order to restore the lost function...
September 2017: Regenerative Engineering and Translational Medicine
https://www.readbyqxmd.com/read/29242243/an-infrared-dye-conjugated-virus-like-particle-for-the-treatment-of-primary-uveal-melanoma
#18
Rhonda C Kines, Isabella Varsavsky, Sanghamitra Choudhary, Debaditya Bhattacharya, Sean Spring, Roger J McLaughlin, Shin J Kang, Hans E Grossniklaus, Demitrios G Vavvas, Stephen Monks, John R MacDougall, Elisabet de Los Pinos, John T Schiller
The work outlined herein describes AU-011, a novel recombinant papillomavirus-like particle (VLP) drug conjugate and its initial evaluation as a potential treatment for primary uveal melanoma. The VLP is conjugated with a phthalocyanine photosensitizer, IRDye 700DX, that exerts its cytotoxic effect through photo-activation with a near-infrared laser. We assessed the anti-cancer properties of AU-011 in vitro utilizing a panel of human cancer cell lines and in vivo using murine subcutaneous and rabbit orthotopic xenograft models of uveal melanoma...
December 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29237830/axl-can-serve-as-entry-factor-for-lassa-virus-depending-on-the-functional-glycosylation-of-dystroglycan
#19
Chiara Fedeli, Giulia Torriani, Clara Galan-Navarro, Marie-Laurence Moraz, Hector Moreno, Gisa Gerold, Stefan Kunz
Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific post-translational modification with the unusual O-linked polysaccharide matriglycan. Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29226950/syndecans-in-chronic-inflammatory-and-autoimmune-diseases-pathological-insights-and-therapeutic-opportunities
#20
REVIEW
Solomon A Agere, Eugene Y Kim, Nahid Akhtar, Salahuddin Ahmed
Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues. There are four mammalian syndecans, SDC-1 thorough 4, which play a critical role in cell adhesion, migration, proliferation, differentiation, and angiogenesis through independent and growth factor mediated signaling. An altered expression of SDCs is often observed in autoimmune disorders, cancer, HIV infection, and many other pathological conditions...
December 11, 2017: Journal of Cellular Physiology
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