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Heparan sulfate

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https://www.readbyqxmd.com/read/28432120/two-glycosaminoglycan-binding-domains-of-the-mouse-cytomegalovirus-encoded-chemokine-mck-2-are-critical-for-oligomerization-of-the-full-length-protein
#1
Sergio M Pontejo, Philip M Murphy
Chemokines are essential for antimicrobial host defenses and tissue repair. Herpesviruses and poxviruses also encode chemokines, copied from their hosts and repurposed for multiple functions, including immune evasion. The CC chemokine MCK-2 encoded by mouse cytomegalovirus (MCMV) has an atypical structure consisting of a classic chemokine domain N-terminal to a second unique domain, resulting from the splicing of MCMV ORFs m131 and m129. MCK-2 is essential for full MCMV infectivity in macrophages and for persistent infection in the salivary gland...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28427941/elongation-affinity-activation-barrier-and-stability-of-a%C3%AE-42-oligomers-fibrils-in-physiological-saline
#2
Roberto A Rodriguez, Liao Y Chen, Germán Plascencia-Villa, George Perry
Amyloid-beta (Aβ) peptides, Aβ40 and the more neurotoxic Aβ42, have been the subject of many research efforts for Alzheimer's disease. In two recent independent investigations, the atomistic structure of Aβ42 fibril has been clearly established in the S-shaped conformation consisting of three β-sheets stabilized by salt bridges formed between the Lys28 sidechain and the C-terminus of Ala42. This structure distinctively differs from the long-known structure of Aβ40 in the β-hairpin shaped conformation consisting of two β-sheets...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28424697/regulation-of-the-functions-of-natural-cytotoxicity-receptors-by-interactions-with-diverse-ligands-and-alterations-in-splice-variant-expression
#3
REVIEW
Tatiana Pazina, Avishai Shemesh, Michael Brusilovsky, Angel Porgador, Kerry S Campbell
The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44, and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and are encoded by the ncr1, ncr2, and ncr3 genes, respectively. NCRs have classically been defined as activating receptors that trigger cytotoxicity and cytokine responses by NK cells upon engaging with ligands on tumor cells. Several new findings, however, have challenged this model and identified alternative mechanisms regulating the function of NCRs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28418018/neurodevelopmental-changes-in-excitatory-synaptic-structure-and-function-in-the-cerebral-cortex-of-sanfilippo-syndrome-iiia-mice
#4
Chrissa A Dwyer, Samantha L Scudder, Ying Lin, Lara E Dozier, Dustin Phan, Nicola J Allen, Gentry N Patrick, Jeffrey D Esko
Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The accumulation of heparan sulfate results in neurological symptoms, culminating in extensive neurodegeneration and early death. To study the impact of storage in postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the enzyme sulfamidase. We show that changes occur in excitatory postsynaptic structure and function in the somatosensory cortex prior to signs of neurodegeneration...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404855/genome-wide-screening-uncovers-the-significance-of-n-sulfation-of-heparan-sulfate-as-a-host-cell-factor-for-chikungunya-virus-infection
#5
Atsushi Tanaka, Uranan Tumkosit, Shota Nakamura, Daisuke Motooka, Natsuko Kishishita, Thongkoon Priengprom, Areerat Sa-Ngasang, Taroh Kinoshita, Naokazu Takeda, Yusuke Maeda
The molecular mechanisms underlying chikungunya virus (CHIKV) infection are poorly characterized. In this study, we analyzed the host factors involved in CHIKV infection using genome-wide screening. Human haploid HAP1 cells, into which an exon-trapping vector was introduced, were challenged with a vesicular stomatitis virus pseudotype bearing the CHIKV E3-E1 envelope proteins. Analysis of genes enriched in the cells resistant to the pseudotyped virus infection unveiled a critical role of N-sulfation of heparan sulfate (HS) for the infectivity of a clinically isolated CHIKV Thai #16856 strain to HAP1 cells...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28402693/heparan-sulfate-proteoglycans-regulate-autophagy-in-drosophila
#6
Claire E Reynolds-Peterson, Na Zhao, Jie Xu, Taryn M Serman, Jielin Xu, Scott B Selleck
Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of signaling and molecular recognition at the cell surface and in the extracellular space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have profound effects on growth, patterning, and cell survival. The Drosophila neuromuscular junction provides a tractable model for understanding the activities of HSPGs at a synapse that displays developmental and activity-dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted the organization of a specialized postsynaptic membrane, the subsynaptic reticulum (SSR), and affected the number and morphology of mitochondria...
April 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28401953/overexpression-of-heparanase-enhances-t-lymphocyte-activities-and-intensifies-the-inflammatory-response-in-a-model-of-murine-rheumatoid-arthritis
#7
Andreas Digre, Kailash Singh, Magnus Åbrink, Rogier M Reijmers, Stellan Sandler, Israel Vlodavsky, Jin-Ping Li
Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401457/comparative-studies-of-vertebrate-iduronate-2-sulfatase-ids-genes-and-proteins-evolution-of-a-mammalian-x-linked-gene
#8
REVIEW
Roger S Holmes
IDS is responsible for the lysosomal degradation of heparan sulfate and dermatan sulfate and linked to an X-linked lysosomal storage disease, mucopolysaccharidosis 2 (MPS2), resulting in neurological damage and early death. Comparative IDS amino acid sequences and structures and IDS gene locations were examined using data from several vertebrate genome projects. Vertebrate IDS sequences shared 60-99% identities with each other. Human IDS showed 47% sequence identity with fruit fly (Drosophila melanogaster) IDS...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28401373/sulfated-glycosaminoglycans-in-protein-aggregation-diseases
#9
REVIEW
Kazuchika Nishitsuji, Kenji Uchimura
Protein aggregation diseases are characterized by intracellular or extracellular deposition of misfolded and aggregated proteins. These aggregated deposits contain multiple proteinaceous and non-protein components that are thought to play critical roles in the etiology and pathogenesis of protein aggregation diseases in vivo. One of these components, the sulfated glycosaminoglycans (GAGs), includes heparan sulfate, chondroitin sulfate, and keratan sulfate. The sulfated GAGs are negatively charged heteropolysaccharides expressed in all mammalian tissues...
April 11, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28397746/non-anticoagulant-heparins-are-hepcidin-antagonists-for-the-treatment-of-anemia
#10
REVIEW
Maura Poli, Michela Asperti, Paola Ruzzenenti, Annamaria Naggi, Paolo Arosio
The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability...
April 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28394734/optimization-of-bioengineered-heparin-heparan-sulfate-production-for-therapeutic-applications
#11
Megan S Lord, MoonSun Jung, John M Whitelock
Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative methods of production of this essential drug. (1) Bioengineering heparin by expressing serglycin in mammalian cells is a promising approach that was recently reported by the authors. (2) This addendum explores the approaches that the authors are taking to increase the yield of recombinantly expressed serglycin decorated with heparin/heparan sulfate focusing on cell culture and bioreactor conditions and proposes that the cell microenvironment is a key modulator of heparin biosynthesis...
April 10, 2017: Bioengineered
https://www.readbyqxmd.com/read/28393899/increased-serum-hyaluronic-acid-and-heparan-sulfate-in-dengue-fever-association-with-plasma-leakage-and-disease-severity
#12
Tommy Hing-Cheung Tang, Sylvie Alonso, Lisa Fong-Poh Ng, Tun-Linn Thein, Vincent Jun-Xiong Pang, Yee-Sin Leo, David Chien-Boon Lye, Tsin-Wen Yeo
Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-α, IL-6, IL-10) were measured on enrollment and convalescence...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28391878/autosomal-dominant-familial-dysbetalipoproteinemia-a-pathophysiological-framework-and-practical-approach-to-diagnosis-and-therapy
#13
REVIEW
Charlotte Koopal, A David Marais, Jan Westerink, Frank L J Visseren
Familial dysbetalipoproteinemia (FD) is a genetic disorder of lipoprotein metabolism associated with an increased risk for premature cardiovascular disease. In about 10% of the cases, FD is caused by autosomal dominant mutations in the apolipoprotein E gene (APOE). This review article provides a pathophysiological framework for autosomal dominant FD (ADFD) and discusses diagnostic challenges and therapeutic options. The clinical presentation and diagnostic work-up of ADFD are illustrated by two cases: a male with premature coronary artery disease and a p...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28389983/single-stage-tandem-mass-spectrometry-assignment-of-the-c-5-uronic-acid-stereochemistry-in-heparan-sulfate-tetrasaccharides-using-electron-detachment-dissociation
#14
Isaac Agyekum, Chengli Zong, Geert-Jan Boons, I Jonathan Amster
The analysis of heparan sulfate (HS) glycosaminoglycans presents many challenges, due to the high degree of structural heterogeneity arising from their non-template biosynthesis. Complete structural elucidation of glycosaminoglycans necessitates the unambiguous assignments of sulfo modifications and the C-5 uronic acid stereochemistry. Efforts to develop tandem mass spectrometric-based methods for the structural analysis of glycosaminoglycans have focused on the assignment of sulfo positions. The present work focuses on the assignment of the C-5 stereochemistry of the uronic acid that lies closest to the reducing end...
April 7, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28388547/involvement-of-heparanase-in-the-pathogenesis-of-acute-kidney-injury-nephroprotective-effect-of-pg545
#15
Zaid Abassi, Shadi Hamoud, Ahmad Hassan, Iyad Khamaysi, Omri Nativ, Samuel N Heyman, Rabia Shekh Muhammad, Neta Ilan, Preeti Singh, Edward Hammond, Gianluigi Zaza, Antonio Lupo, Maurizio Onisto, Gloria Bellin, Valentina Masola, Israel Vlodavsky, Giovani Gambaro
Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387673/upregulated-expression-of-heparanase-and-heparanase-2-in-the-brains-of-alzheimer-s-disease
#16
Beatriz García, Carla Martín, Olivia García-Suárez, Bárbara Muñiz-Alonso, Helena Ordiales, Santiago Fernández-Menéndez, Jorge Santos-Juanes, Laura Lorente-Gea, Sonia Castañón, Ikerne Vicente-Etxenausia, Kelvin Manuel Piña Batista, Irune Ruiz-Díaz, María Cristina Caballero-Martínez, Jesús Merayo-Lloves, Isabel Guerra-Merino, Luis M Quirós, Iván Fernández-Vega
BACKGROUND: Heparan sulfate proteoglycans (HSPGs) promote amyloid-β peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity. OBJECTIVE: To analyze HPSE and HPSE2 expressions at different stages of AD. METHODS: RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain...
April 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28386074/the-role-of-heparanase-in-the-pathogenesis-of-acute-pancreatitis-a-potential-therapeutic-target
#17
Iyad Khamaysi, Preeti Singh, Susan Nasser, Hoda Awad, Yehuda Chowers, Edmond Sabo, Edward Hammond, Ian Gralnek, Irena Minkov, Alessandro Noseda, Neta Ilan, Israel Vlodavsky, Zaid Abassi
Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381397/cd138-mediates-selection-of-mature-plasma-cells-by-regulating-their-survival
#18
Mark J McCarron, Pyong Woo Park, David R Fooksman
Antibody secreting cells (ASCs) are critical effector cells and long-lived sentinels for immune memory. ASCs are highly dependent on exogenous soluble factors such as IL-6 and APRIL, to prevent their cell death. We have found that the canonical surface marker of ASCs, CD138 (syndecan-1), which is upregulated during ASC maturation, is required in a cell-intrinsic manner to mount an effective long-term humoral immune response following immunization. Surface expression of CD138 increased heparan sulfate levels on ASCs, which are known to bind pro-survival cytokines, leading to increased survival in a cell-intrinsic manner in vivo...
April 5, 2017: Blood
https://www.readbyqxmd.com/read/28371070/molecular-analysis-of-a-novel-intragenic-deletion-in-gpc3-in-three-cousins-with-simpson-golabi-behmel-syndrome
#19
Julia Schmidt, Ronja Hollstein, Frank J Kaiser, Gabriele Gillessen-Kaesbach
Simpson-Golabi-Behmel syndrome (SGBS) is characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features intellectual disability (ID) of variable degree, and an increased risk for embryonal tumors. SGBS is X-linked recessive and caused by deletions, duplications, and point mutations in GPC3, encoding a membrane associated cell surface heparan sulfate proteoglycan named glypican 3. GPC3 plays essential roles in the regulation of cell growth signaling and cell division...
March 29, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28359266/identification-of-novel-class-of-triazolo-thiadiazoles-as-potent-inhibitors-of-human-heparanase-and-their-anticancer-activity
#20
C P Baburajeev, Chakrabhavi Dhananjaya Mohan, Shobith Rangappa, Daniel J Mason, Julian E Fuchs, Andreas Bender, Uri Barash, Israel Vlodavsky, Basappa, Kanchugarakoppal S Rangappa
BACKGROUND: Expression and activity of heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is associated with progression and poor prognosis of many cancers which makes it an attractive drug target in cancer therapeutics. METHODS: In the present work, we report the in vitro screening of a library of 150 small molecules with the scaffold bearing quinolones, oxazines, benzoxazines, isoxazoli(di)nes, pyrimidinones, quinolines, benzoxazines, and 4-thiazolidinones, thiadiazolo[3,2-a]pyrimidin-5-one, 1,2,4-triazolo-1,3,4-thiadiazoles, and azaspiranes against the enzymatic activity of human heparanase...
March 31, 2017: BMC Cancer
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