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https://www.readbyqxmd.com/read/29752409/specific-glycosaminoglycan-chain-length-and-sulfation-patterns-are-required-for-cell-uptake-of-tau-vs-%C3%AE-synuclein-and-%C3%AE-amyloid-aggregates
#1
Barbara E Stopschinski, Brandon B Holmes, Gregory M Miller, Victor A Manon, Jaime Vaquer-Alicea, William L Prueitt, Linda C Hsieh-Wilson, Marc I Diamond
Transcellular propagation of protein aggregate "seeds" has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct binding to modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs)...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29747357/-research-on-the-effect-of-biological-glue-on-augmenting-the-viscosity-of-tissue-engineering-retinal-nerve-scaffolds
#2
K J Li, S J Yang, K Li, Y T Wei, J Zhuang, Y H Zhuo, J Ge
Objective: To evaluate the adhesion effect of tissue engineering retinal nerve scaffolds modified with biological glue. Methods: Experimental study. To fabricate a biological glue by blending laminin, collagen Ⅳ, entactin and HSPG(2) with phosphate-buffered saline (PBS) buffer solution, scaffolds were then modified with the biological glue of various concentration levels (10 μl/cm(2), 20 μl/cm(2), 30 μl/cm(2) and 40 μl/cm(2)). The effects of various concentration levels glue on inducing scaffold adhesion were analyzed after 24 h...
April 11, 2018: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29740281/heparan-sulfate-proteoglycans-as-drivers-of-neural-progenitors-derived-from-human-mesenchymal-stem-cells
#3
Rachel K Okolicsanyi, Lotta E Oikari, Chieh Yu, Lyn R Griffiths, Larisa M Haupt
Background: Due to their relative ease of isolation and their high ex vivo and in vitro expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation. Methods: Following the determination that hMSCs maintain neural potential throughout extended in vitro expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29726297/glioma-targeting-peptide-modified-apoferritin-nanocage
#4
Meifang Zhai, Yuli Wang, Ligang Zhang, Meng Liang, Shiyao Fu, Lin Cui, Meiyan Yang, Wei Gong, Zhiping Li, Lian Yu, Xiangyang Xie, Chunrong Yang, Yang Yang, Chunsheng Gao
Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature of drugs and the physiological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). An ideal glioma-targeted delivery system must be sufficiently potent to cross the BBB and BBTB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29688404/heparan-sulfate-proteoglycan-sulfation-regulates-uterine-differentiation-and-signaling-during-embryo-implantation
#5
Yan Yin, Adam Wang, Li Feng, Yu Wang, Hong Zhang, Ivy Zhang, Brent Bany, Liang Ma
To prepare for embryo implantation, uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs)...
April 23, 2018: Endocrinology
https://www.readbyqxmd.com/read/29673857/crystalline-silica-alters-sulfatase-1-expression-in-rat-lungs-which-influences-hyper-proliferative-and-fibrogenic-effects-in-human-lung-epithelial-cells
#6
Timothy N Perkins, Paul M Peeters, Catrin Albrecht, Roel P F Schins, Mieke A Dentener, Brooke T Mossman, Emiel F M Wouters, Niki L Reynaert
Lung epithelial cells are the first cell-type to come in contact with hazardous dust materials. Upon deposition, they invoke complex reactions in attempt to eradicate particles from the airways, and repair damage. The cell surface is composed of a heterogeneous network of matrix proteins and proteoglycans, which act as scaffold and control cell-signaling networks. These functions are controlled, in part, by the sulfation patterns of heparin-sulfate proteoglycans (HSPGs), which are enzymatically regulated. Although there is evidence of altered HSPG-sulfation in idiopathic pulmonary fibrosis (IPF), this is not investigated in silicosis...
April 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29621420/regulation-of-eosinophil-recruitment-and-allergic-airway-inflammation-by-heparan-sulfate-proteoglycan-hspg-modifying-enzymes
#7
Xiao Na Ge, Idil Bastan, Sung Gil Ha, Yana G Greenberg, Jeffrey D Esko, Savita P Rao, P Sriramarao
BACKGROUND: HSPGs are glycoproteins containing covalently attached heparan sulfate (HS) chains which bind to growth factors, chemokines, etc., and regulate various aspects of inflammation including cell recruitment. We previously showed that deletion of endothelial N-acetylglucosamine N-deacetylase-N-sulfotransferase-1 (Ndst1), an enzyme responsible for N-sulfation during HS biosynthesis, reduces allergic airway inflammation (AAI). Here, we investigated the importance of O-sulfation mediated by uronyl 2-O-sulfotransferase (Hs2st) in development of AAI relative to N-sulfation...
April 5, 2018: Experimental Lung Research
https://www.readbyqxmd.com/read/29593032/extracellular-conformational-changes-in-the-capsid-of-human-papillomaviruses-contribute-to-asynchronous-uptake-into-host-cells
#8
Miriam Becker, Lilo Greune, M Alexander Schmidt, Mario Schelhaas
The human papillomavirus type 16 (HPV16) is the leading cause of cervical cancer. For initial infection, HPV16 utilizes a novel endocytic pathway for host cell entry. Unique amongst viruses, uptake occurs asynchronously over a protracted period of time with half-times between 9-12 h. To trigger endocytic uptake, the virus particles need to undergo a series of structural modifications after initial binding to heparan sulfate proteoglycans (HSPG). These changes involve proteolytic cleavage of the major capsid protein L1 by kallikrein-8 (KLK8), exposure of the N-terminus of the minor capsid protein L2 by cyclophilins, and cleavage of this N-terminus by furin...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29559501/synaptogenesis-is-modulated-by-heparan-sulfate-in-caenorhabditis-elegans
#9
María Lázaro-Peña, Carlos Díaz-Balzac, Hannes Bülow, Scott Emmons
The nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in C. elegans It is composed of sequential steps that are governed by more than 3,000 chemical connections. Here we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. HS, sulfated in position 3 by the HS modification enzyme HST-3.1 / HS 3- O -sulfotransferase and attached to the HSPG glypicans LON-2/glypican and GPN-1/glypican, functions cell-autonomously and non-autonomously for response to hermaphrodite contact during mating...
March 20, 2018: Genetics
https://www.readbyqxmd.com/read/29518749/sglt2-inhibition-reduces-atherosclerosis-by-enhancing-lipoprotein-clearance-in-ldlr-type-1-diabetic-mice
#10
Annas Al-Sharea, Andrew J Murphy, L A Huggins, Y Hu, Ira J Goldberg, Prabhakara R Nagareddy
BACKGROUND AND AIMS: Leukocytosis, particularly monocytosis, has been shown to promote atherosclerosis in both diabetic and non-diabetic mouse models. We previously showed that hyperglycemia independently promotes monocytosis and impairs the resolution of atherosclerosis. Since patients with chronic diabetes often develop dyslipidemia and also have increased risk for atherosclerosis, we sought to examine how controlling blood glucose affects atherosclerosis development in the presence of severe hyperlipidemia...
April 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29499356/a-role-for-proteoglycans-in-vascular-disease
#11
REVIEW
Thomas N Wight
The content of proteoglycans (PGs) is low in the extracellular matrix (ECM) of vascular tissue, but increases dramatically in all phases of vascular disease. Early studies demonstrated that glycosaminoglycans (GAGs) including chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) accumulate in vascular lesions in both humans and in animal models in areas of the vasculature that are susceptible to disease initiation (such as at branch points) and are frequently coincident with lipid deposits...
February 27, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29434536/heparan-sulfate-proteoglycans-as-emerging-players-in-synaptic-specificity
#12
REVIEW
Giuseppe Condomitti, Joris de Wit
Neural circuits consist of distinct neuronal cell types connected in specific patterns. The specificity of these connections is achieved in a series of sequential developmental steps that involve the targeting of neurites, the identification of synaptic partners, and the formation of specific types of synapses. Cell-surface proteins play a critical role in each of these steps. The heparan sulfate proteoglycan (HSPG) family of cell-surface proteins is emerging as a key regulator of connectivity. HSPGs are expressed throughout brain development and play important roles in axon guidance, synapse development and synapse function...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29415062/loss-of-intra-islet-heparan-sulfate-is-a-highly-sensitive-marker-of-type-1-diabetes-progression-in-humans
#13
Charmaine J Simeonovic, Sarah K Popp, Lora M Starrs, Debra J Brown, Andrew F Ziolkowski, Barbara Ludwig, Stefan R Bornstein, J Dennis Wilson, Alberto Pugliese, Thomas W H Kay, Helen E Thomas, Thomas Loudovaris, Fui Jiun Choong, Craig Freeman, Christopher R Parish
Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are progressively destroyed. Clinical trials of immunotherapies in recently diagnosed T1D patients have only transiently and partially impacted the disease course, suggesting that other approaches are required. Our previous studies have demonstrated that heparan sulfate (HS), a glycosaminoglycan conventionally expressed in extracellular matrix, is present at high levels inside normal mouse beta cells. Intracellular HS was shown to be critical for beta cell survival and protection from oxidative damage...
2018: PloS One
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
#14
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...
March 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29301346/blood-coagulation-factor-x-exerts-differential-effects-on-adenovirus-entry-into-human-lymphocytes
#15
James S Findlay, Graham P Cook, G Eric Blair
It has been proposed that blood coagulation factors, principally factor X (FX), enhance the uptake of human adenovirus type 5 (Ad5) into cultured epithelial cells by bridging the viral hexon capsid protein and cell-surface heparan sulphate proteoglycans (HSPGs). We studied the effects of FX on Ad transduction of lymphoid cell lines (NK92MI, a natural killer cell line; Daudi, a B-cell line and Jurkat, a T-cell line) as well as primary peripheral blood lymphocytes (PBL) and HeLa epithelial cells using either replication-deficient Ad5, or a derivative in which the Ad5 fiber was replaced with that of another Ad type, Ad35, termed Ad5F35...
January 3, 2018: Viruses
https://www.readbyqxmd.com/read/29251725/broad-spectrum-non-toxic-antiviral-nanoparticles-with-a-virucidal-inhibition-mechanism
#16
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...
February 2018: Nature Materials
https://www.readbyqxmd.com/read/29242243/an-infrared-dye-conjugated-virus-like-particle-for-the-treatment-of-primary-uveal-melanoma
#17
Rhonda C Kines, Isabella Varsavsky, Sanghamitra Choudhary, Debaditya Bhattacharya, Sean Spring, Roger McLaughlin, Shin J Kang, Hans E Grossniklaus, Demetrios 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 photoactivation with a near-infrared laser. We assessed the anticancer 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...
February 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29226950/syndecans-in-chronic-inflammatory-and-autoimmune-diseases-pathological-insights-and-therapeutic-opportunities
#18
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
https://www.readbyqxmd.com/read/29212806/syndecan-1-promotes-wnt-%C3%AE-catenin-signaling-in-multiple-myeloma-by-presenting-wnts-and-r-spondins
#19
Zemin Ren, Harmen van Andel, Wim de Lau, Robin B Hartholt, Madelon M Maurice, Hans Clevers, Marie José Kersten, Marcel Spaargaren, Steven T Pals
Multiple myeloma (MM) is characterized by the expansion of malignant plasma cells in the bone marrow (BM). Most MMs display aberrant Wnt/β-catenin signaling, which drives proliferation; however, they lack oncogenic Wnt pathway mutations, suggesting activation by autocrine Wnt ligands and/or paracrine Wnts from the BM microenvironment. Expression of the heparan sulfate (HS) proteoglycan syndecan-1 is a hallmark of MM. Syndecan-1 is a critical player in the complex reciprocal interaction between MM cells and their BM niche, mediating growth factor/cytokine binding and signaling by its HS chains...
March 1, 2018: Blood
https://www.readbyqxmd.com/read/29151984/hepatic-and-aortic-arch-expression-and-serum-levels-of-syndecan-1-in-apoe-mice
#20
Elena I Leonova, Elena S Sadovnikova, Elvira R Shaykhutdinova, Oxana V Galzitskaya, Arkady N Murashev, Alexandr S Solonin
Background: Heparan sulfate proteoglycan (HSPG) syndecan-1 (Sdc1) acts as a receptor for triglyceride-rich lipoproteins (TRLs), growth factors, chemokines and enzymes. Due to the disordered structure, its function is as diverse as its ligands. In this paper, we have analyzed hepatic and aortic arch expression of Sdc1 in ApoE-/- mice and examined their association with biochemical changes in plasma during the atheroma formation. Methods: ApoE knockout (ApoE-/- ) mice as a model of atherosclerosis were used...
2017: Open Biochemistry Journal
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