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Heparan sulfate

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https://www.readbyqxmd.com/read/28813681/uncoupling-the-mitogenic-and-metabolic-functions-of-fgf1-by-tuning-fgf1-fgf-receptor-dimer-stability
#1
Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J Conklin, Thomas A Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1(ΔHBS)) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1(ΔHBS) exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28811133/arylamidonaphtalene-sulfonate-compounds-as-a-novel-class-of-heparanase-inhibitors
#2
Riccardo Rondanin, Sara Fochi, Riccardo Baruchello, Tatiana Bernardi, Paola Oliva, Floriana Semeraro, Daniele Simoni, Giuseppe Giannini
The search for antimetastatic agents for cancer therapy may involve the ability of new compounds to maintain the tissue extracellular matrix integrity. Among known factors, heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, is a promising target whose inhibition could represent a strong obstacle for metastatic cancerous mechanisms. The antimetastatic activity of some suramin derivatives reported in literature suggests a possible involvement of the heparanase enzyme. To confirm such hypothesis, we have investigated FCE27266, a molecule known for its antiangiogenic and antimetastatic properties...
August 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28810553/evaluation-of-the-c-domain-of-heparanase-during-age-induced-macrophage-inflammatory-response
#3
Qiaojing Qin, Guang Xu, Weiwei Qi, Mei Guo, Zhaoxia Wang, Wangjie Xu, Zhongdong Qiao, Yong Gu, Jianying Niu
Diabetic vasculopathy is intensified by macrophage inflammation caused by advanced glycation end products (AGEs). Heparanase (HPA) is a unique endoglycosidase, which cleaves heparan sulfate proteoglycans (HSPGs) including syndecan-1 (Syn-1) to further stimulate macrophage cell migration and inflammation. The present study was planned to evaluated the role of C-domain (if any) of HPA in AGE inflammatory response in macrophages. Cell viability was assessed using MTT assay, migration assay, ELISA for tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, mRNA expression by RT-PCR and heparan degrading enzyme assay for HPA activity...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28806774/fibroblast-growth-factor-receptor-1-mediates-internalization-of-pathogenic-spotted-fever-rickettsiae-into-host-endothelium
#4
Abha Sahni, Jignesh Patel, Hema P Narra, Casey L C Schroeder, David H Walker, Sanjeev K Sahni
Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28799166/the-molecular-mechanism-underlying-unconventional-secretion-of-fibroblast-growth-factor-2-from-tumor-cells
#5
REVIEW
Julia P Steringer, Walter Nickel
Fibroblast Growth Factor 2 (FGF2) is a potent cell survival factor involved in tumor induced angiogenesis. FGF2 is secreted from cells through an unconventional secretory mechanism based upon direct translocation across the plasma membrane. The molecular mechanism underlying this process depends on a surprisingly small set of trans-acting factors that are physically associated with the plasma membrane. FGF2 membrane translocation is mediated by the ability of FGF2 to oligomerize and to insert into the plasma membrane in a PI(4,5)P2 dependent manner...
August 10, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28795878/effects-of-prisma%C3%A2-skin-dermal-regeneration-device-containing-glycosaminoglycans-on-human-keratinocytes-and-fibroblasts
#6
Raffaella Belvedere, Valentina Bizzarro, Luca Parente, Francesco Petrella, Antonello Petrella
Prisma® Skin is a new pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. It includes alginates, hyaluronic acid and mainly mesoglycan. The latter is a natural glycosaminoglycan preparation containing chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin and it is used in the treatment of vascular disease. Glycosaminoglycans may contribute to the re-epithelialization in the skin wound healing, as components of the extracellular matrix. Here we describe, for the first time, the effects of Prisma® Skin in in vitro cultures of adult epidermal keratinocytes and dermal fibroblasts...
August 10, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28783314/deciphering-the-role-of-sulfonated-unit-in-heparin-mimicking-polymer-to-promote-neural-differentiation-of-escs
#7
Jiehua Lei, Yuqi Yuan, Zhonglin Lyu, Mengmeng Wang, Qi Liu, Hongwei Wang, Lin Yuan, Hong Chen
Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS) hold great potential for inducing the neural differentiation of embryonic stem cells (ESCs) and have brought new hope for the treatment of neurological diseases. However, the disadvantages of natural heparin/HS, such as difficulty in isolating with a sufficient amount, highly heterogeneous in structure, the risk of immune responses, have limited their further therapeutic applications. Thus, there is a great demand for stable, controllable and well-defined synthetic alternatives of heparin/HS with more effective biological functions...
August 7, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28770943/insights-into-the-role-of-3-o-sulfotransferase-in-heparan-sulfate-biosynthesis
#8
Maria Cecília Zorél Meneghetti, Tarsis Gesteira Ferreira, Alexandre Keiji Tashima, Suely F Chavante, Edwin Alexander Yates, Jian Liu, Helena Bonciani Nader, Marcelo A Lima
3-O-Sulfotransferase enzyme (sHS) from Litopenaeus vannamei was cloned and its substrate specificity was investigated against a number of GAG structures, including modified heparin polysaccharides and model oligosaccharides. For the heparin polysaccharides, derived from porcine intestinal mucosa heparin, sulfate groups were incorporated into glucosamine residues containing both N-sulfated and N-acetylated substitution within the regions of the predominant repeating disaccharide, either I-ANS or I-ANAc. However, the resulting polysaccharides did not stabilize antithrombin, which is correlated with anticoagulant activity...
August 16, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28768899/aberrant-perichondrial-bmp-signaling-mediates-multiple-osteochondromagenesis-in-mice
#9
Toshihiro Inubushi, Satoshi Nozawa, Kazu Matsumoto, Fumitoshi Irie, Yu Yamaguchi
Multiple hereditary exostoses (MHE) is characterized by the development of numerous benign bony tumors (osteochondromas). Although it has been well established that MHE is caused by mutations in EXT1 and EXT2, which encode glycosyltransferase essential for heparan sulfate (HS) biosynthesis, the cellular origin and molecular mechanisms of MHE remain elusive. Here, we show that in Ext1 mutant mice, osteochondromas develop from mesenchymal stem cell-like progenitor cells residing in the perichondrium, and we show that enhanced BMP signaling in these cells is the primary signaling defect that leads to osteochondromagenesis...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28766595/design-synthesis-and-evaluation-of-heparan-sulfate-mimicking-glycopolymers-for-inhibiting-heparanase-activity
#10
Ravi S Loka, Fei Yu, Eric T Sletten, Hien M Nguyen
Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics...
August 10, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28762851/concentration-of-sulfated-glycosaminoglycans-in-the-mammary-tissue-of-female-rats-with-the-aging-and-about-hormonal-influence
#11
Sueli M P S Torres, Helena B Nader, Ricardo S Simões, Edmund C Baracat, Manuel de J Simões, Luiz F P Fuchs, José Maria Soares-Jr, Regina Célia T Gomes
It was to evaluate the concentration of sulfate glycosaminoglycans (GAG) in mammary tissue of the young and adult female rats and ovariectomized females rats after hormonal stimulation. For this purpose, 60 female rats were divided into six groups with 10 animals/each: nonovariectomized groups: G1 (5 months), and G2 (15 months) and ovariectomized groups: OG (vehicle); EG: (estradiol, 7 days of treatment), PG (progesterone acetate, 23 days of treatment) and EPG: (estradiol (7 days of treatment) and next progesterone acetate (23 days of treatment)...
August 1, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28762182/diet-induced-hypercholesterolemia-alters-liver-glycosaminoglycans-and-associated-lipoprotein-receptors-in-rats
#12
Gangappa Kiran, Ummiti J S Prasada Rao, Paramahans V Salimath, Nandini D Chilkunda
Glycosaminoglycans (GAGs) play an important role in lipoprotein metabolism. In liver, it facilitates the uptake of remnants through receptor-independent endocytosis. However, changes in liver GAGs during diet-induced hypercholesterolemia with normal levels of fat feeding are unknown. Present paper highlights the effect of diet-induced hypercholesterolemia with normal levels (5%) of fat on liver GAGs and other associated lipoprotein receptors. Hypercholesterolemia was induced in rats by feeding diet supplemented with 0...
July 31, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28761422/heparan-sulfate-proteoglycans-and-heparanases-in-alzheimer-s-disease-current-outlook-and-potential-therapeutic-targets
#13
Laura Lorente-Gea, Beatriz García, Carla Martín, Luis M Quirós, Iván Fernández-Vega
No abstract text is available yet for this article.
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28757565/the-pharmaceutical-device-prisma-%C3%A2-skin-promotes-in-vitro-angiogenesis-through-endothelial-to-mesenchymal-transition-during-skin-wound-healing
#14
Raffaella Belvedere, Valentina Bizzarro, Luca Parente, Francesco Petrella, Antonello Petrella
Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma(®) Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma(®) Skin which mediate the activation of the pathway triggered by CD44 receptor...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28756657/versatile-separation-and-analysis-of-heparan-sulfate-oligosaccharides-using-graphitized-carbon-liquid-chromatography-and-electrospray-mass-spectrometry
#15
Rebecca L Miller, Scott E Guimond, Mark Prescott, Jeremy E Turnbull, Niclas Karlsson
Heparin and heparan sulfate (HS) by nature contain multiple isomeric structures, which are fundamental for the regulation of biological processes. Here we report the use of a porous graphitized carbon (PGC) LC-MS method with effective separation and sensitivity to separate mixtures of digested HS oligosaccharides. Application of this method allowed the separation of oligosaccharide mixtures with various degree of polymerization (dp) ranging from dp4 to dp8, two dp4 isomers that were baseline resolved, four dp6 isomers, and the observation of a dp3 oligosaccharide...
August 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28755756/brain-extracellular-space-the-final-frontier-of%C3%A2-neuroscience
#16
REVIEW
Charles Nicholson, Sabina Hrabětová
Brain extracellular space is the narrow microenvironment that surrounds every cell of the central nervous system. It contains a solution that closely resembles cerebrospinal fluid with the addition of extracellular matrix molecules. The space provides a reservoir for ions essential to the electrical activity of neurons and forms an intercellular chemical communication channel. Attempts to reveal the size and structure of the extracellular space using electron microscopy have had limited success; however, a biophysical approach based on diffusion of selected probe molecules has proved useful...
July 26, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28753105/the-vascular-basement-membrane-in-the-healthy-and-pathological-brain
#17
Maj S Thomsen, Lisa J Routhe, Torben Moos
The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28751108/processing-of-mutant-n-acetyl-%C3%AE-glucosaminidase-in-mucopolysaccharidosis-type-iiib-fibroblasts-cultured-at-low-temperature
#18
O L M Meijer, H Te Brinke, R Ofman, L IJlst, F A Wijburg, N van Vlies
BACKGROUND: The autosomal recessive, neurodegenerative disorder mucopolysaccharidosis type IIIB (MPSIIIB) is caused by a deficiency of the lysosomal enzyme N-acetyl-α-glucosaminidase (NAGLU), resulting in accumulation of heparan sulfate. The disease spectrum comprises a severe, rapidly progressing (RP) phenotype and a more attenuated, slowly progressing (SP) phenotype. Previous studies showed significantly higher NAGLU activity in skin fibroblasts of SP patients when cultured at 30°C which may be relevant for development of novel therapeutic strategies...
July 12, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28747756/combinatorial-extracellular-matrix-microenvironments-for-probing-endothelial-differentiation-of-human-pluripotent-stem-cells
#19
Luqia Hou, Joseph J Kim, Maureen Wanjare, Bhagat Patlolla, John Coller, Vanita Natu, Trevor J Hastie, Ngan F Huang
Endothelial cells derived from human pluripotent stem cells are a promising cell type for enhancing angiogenesis in ischemic cardiovascular tissues. However, our understanding of microenvironmental factors that modulate the process of endothelial differentiation is limited. We examined the role of combinatorial extracellular matrix (ECM) proteins on endothelial differentiation systematically using an arrayed microscale platform. Human pluripotent stem cells were differentiated on the arrayed ECM microenvironments for 5 days...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745308/coxsackievirus-a16-utilizes-cell-surface-heparan-sulfate-glycosaminoglycans-as-its-attachment-receptor
#20
Xueyang Zhang, Jinping Shi, Xiaohua Ye, Zhiqiang Ku, Chao Zhang, Qingwei Liu, Zhong Huang
Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for hand, foot and mouth disease, which affects more than two million children in the Asian-Pacific region annually. Previous studies have shown that scavenger receptor B2 is a functional receptor for CVA16 that facilitates the uncoating process. However, it remains unclear whether other receptors are required for efficient CVA16 infection. In this study, by using a variety of assays we demonstrated that CVA16 utilizes surface heparan sulfate glycosaminoglycans as its attachment receptor...
July 26, 2017: Emerging Microbes & Infections
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