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Youngsil Choi, Mi-Jung Kwon, Yangmi Lim, Ji-Hye Yun, Weontae Lee, Eok-Soo Oh
Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to interact through their transmembrane domains to form non-covalently linked homodimers, a process essential for their individual functions. Because all syndecan transmembrane domains are highly conserved and thus might mediate interactions between different members of the syndecan family, we investigated syndecan interactions in detail. All recombinant syndecan-2 and -4 protein variants containing the transmembrane domain formed not only sodium dodecyl sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers...
July 3, 2015: Journal of Biological Chemistry
V A Mit'kevich, A A Makarov, O N Il'inskaia
Some ribonucleases (RNases) produce selective toxic effect on the cancer cells. The mechanism of this antitumor activity remains largely unclear. The subject of this review is the RNases interaction with cellular components, resulting in the induction of apoptosis of tumor cells. Cell surface structures, which are potential acceptors of the exogenous RNase are discussed: acidic lipids and glycoproteins, heparansulfate-containing proteoglycans, actin, and RNA-associated proteins. Cell membranes of normal and malignant cells differ according to the composition of these components, which largely determines the selectivity of RNases for the latter...
March 2014: Molekuliarnaia Biologiia
U Lindner, J Kramer, J Behrends, N-O Wendler, H Lehnert, J Rohwedel, P Schlenke
No abstract text is available yet for this article.
2010: Journal of Stem Cells & Regenerative Medicine
Tatiana Y Prudnikova, Nikolaos Soulitzis, Olesya S Kutsenko, Lyudmila A Mostovich, Klas Haraldson, Ingemar Ernberg, Vladimir I Kashuba, Demetrios A Spandidos, Eugene R Zabarovsky, Elvira V Grigorieva
Heparansulfate proteoglycans (HSPG) play an important role in cell-cell and cell-matrix interactions and signaling, and one of the key enzymes in heparansulfate biosynthesis is d-glucuronyl C5-epimerase (GLCE). A tumor suppressor function has been demonstrated for GLCE in breast and lung carcinogenesis; however, no data are available as to the expression and regulation of the gene in prostate cancer. In this study, decreased GLCE expression was observed in 10% of benign prostate hyperplasia (BPH) tissues and 53% of prostate tumors, and increased GLCE mRNA levels were detected in 49% of BPH tissues and 21% of tumors...
October 2013: Cancer Medicine
Yunliang Chen, Michael Scully, Gloria Dawson, Christopher Goodwin, Min Xia, Xinjie Lu, Ajay Kakkar
Heparansulfate-proteoglycans (HSPGs) interact via their polyanionic heparansulfate (HS) side chains with a variety of proteins on the cell surface or within the extracellular matrix membrane. The large number of heparin/HS binding proteins form a highly interconnected functional network, which has been termed as the heparin/HS interactome and is functionally linked to physiological and pathological processes. The aim of this study was to investigate the global effect of these protein-HSPG interactions on the tumourigenicity of two breast cancer cell lines (MCF-7 and MDA-MB-231)...
June 4, 2013: Thrombosis and Haemostasis
Antigony Mitselou, Urania Skoufi, Konstantinos E Tsimogiannis, Evagelos Briasoulis, Theodoros Vougiouklakis, Dimitris Arvanitis, Elli Ioachim
Syndecan-1 is a transmembrane heparansulfate proteoglycan, which regulates cell proliferation, migration, angiogenesis, cell-to-cell and cell-to-extracellular matrix adhesion and may influence malignant cell behavior. We investigated the alterations of syndecan-1 expression in colorectal cancer and analyzed the relationship between clinicopathological parameters, proliferation indices, angiogenic markers, and extracellular matrix components. Syndecan-1 protein expression observed in the tumorous epithelium was high in 52/97 (53...
September 2012: Anticancer Research
P Berger, K Ballmer-Hofer
Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel formation through activation of the type V receptor tyrosine kinases VEGFR-1, -2 and -3. In addition, VEGFs interact with co-receptors such as neuropilins, integrins, semaphorins or heparansulfate glycosaminoglycans. Ligand binding dimerises the receptors and activates their intracellular tyrosine kinase domains, resulting in phosphorylation of tyrosine residues acting as docking sites for intracellular signalling molecules. Ligand-induced receptor is internalised and then transported through early, late, and recycling endosomes, and finally degraded by proteasomal or lysosomal pathways...
December 15, 2011: Swiss Medical Weekly
I Valociková
Diabetic nephropathy (DN) is the most serious, life limited complication of both types of diabetes mellitus. Therefore the early identification and intensive treatment of DN is very important. DN involves the thickening of glomerular basement membrane (GBM) and the depletion of glycosaminoglycan (GAG) in the GBM with resultant diminution in the physiological electrostatic charge barrier. Additional mechanism in pathophysiology of DN is mesangial expansion. Sulodexide is glycosaminoglycan mixture of heparansulfate and dermatan sulfate...
May 2011: Vnitr̆ní Lékar̆ství
Ruth Eissler, Christoph Schmaderer, Krisztina Rusai, Louisa Kühne, Daniel Sollinger, Tobias Lahmer, Oliver Witzke, Jens Lutz, Uwe Heemann, Marcus Baumann
Hypertension causes cardiac hypertrophy characterized by low-grade inflammation. Toll-like receptors (TLRs), members of the innate immune system, contribute to cardiac failure. We hypothesized that hypertension is accompanied by enhanced TLR4 expression and activity. Cardiac TLR4 expression was determined in untreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY; 4, 8, 16 weeks). Besides, hearts of 8-week-old rats were stimulated with the endogenous TLR4 ligand heparansulfate (HS); the proinflammatory mRNA pattern was assessed (tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1)...
May 2011: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Petra Fallier-Becker, Jan Sperveslage, Hartwig Wolburg, Susan Noell
Astrocytic endfeet membranes are studded with aquaporin-4 (AQP4) containing orthogonal arrays of particles (OAP) which can be visualized exclusively by the freeze-fracturing method. They are predominantly expressed where the astroglial membrane is in contact with the superficial and perivascular basal lamina. This polarity seems to be essential for the integrity of the blood-brain barrier (BBB). The basal lamina containing many extracellular matrix (ECM) components such as collagen, laminin and heparansulfate proteoglycans like agrin is thought to influence this OAP-related polarity of astrocytes...
January 7, 2011: Brain Research
Tatiana Y Prudnikova, Liudmila A Mostovich, Natalia V Domanitskaya, Tatiana V Pavlova, Vladimir I Kashuba, Eugene R Zabarovsky, Elvira V Grigorieva
BACKGROUND: D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in the biosynthesis of heparansulfate proteoglycans. Down-regulation of GLCE expression in human breast tumours suggests a possible involvement of the gene in carcinogenesis. In this study, an effect of GLCE ectopic expression on cell proliferation and viability of breast carcinoma cells MCF7 in vitro and its potential molecular mechanisms were investigated. RESULTS: D-glucuronyl C5-epimerase expression was significantly decreased in MCF7 cells compared to normal human breast tissue...
2010: Cancer Cell International
Johannes Bühligen, Mirko Himmel, Carl Gebhardt, Jan C Simon, Wolfgang Ziegler, Marco Averbeck
Following antigen contact, maturation and migration of DCs into lymphatic tissues are crucial to the developing immune response or maintenance of tolerance. Lysophosphatidylcholine (LysoPC) is generated during apoptosis of cells and acts as a "find-and-eat-me" signal thought to prevent autoimmunity. Moreover, LysoPC can activate PKCδ and initiates a signaling cascade that leads to phosphorylation and inactivation of syndecan-4 (SDC4), a heparansulfate proteoglycan integrin co-receptor. In human monocyte-derived DCs, we recently demonstrated that SDC4 is upregulated during maturation thereby stimulating DC motility...
November 2010: Journal of Cellular Physiology
Sojoong Choi, Hawon Lee, Jung Ran Choi, Eok Soo Oh
Syndecans, cell surface heparansulfate proteoglycans, have been proposed to act as cell surface receptors and/or coreceptors to play critical roles in multiple cellular functions. However, recent reports suggest that the function of syndecans can be further extended through shedding, a cleavage of extracellular domain. Shedding constitutes an additional level for controlling the function of syndecans, providing a means to attenuate and/or regulate amplitude and duration of syndecan signals by modulating the activity of syndecans as cell surface receptors...
May 2010: BMB Reports
A V Serbin, E N Karaseva, N E Fedorova, M V Pavlova, E V Klimova, M V Leont'eva, A A Kushch
The artificial polycarboxyacidic compounds (PC), imitating the principle of furan-derived and negatively charged structures alternating in the polymeric backbone of nucleic acids, previously explored as interferon inductors and stimulators of antiviral immunity in vivo, were modified by the side groups to amplify the direct antiviral potency in vitro and investigated in the cell culture model of human diploid fibroblasts infected with human cytomegalovirus (CMV) in a microbicidal scheme. Reconstruction from the PC to membrane potent compounds (MPC) was carried out by covalent modification with lipotropic pharmacophores (of cage-hydrocarbon structures similar to rimantadine or camphor-like terpenoids), as well as by conversion of the carboxy groups to sulfate-anionic derivates, related to the CMV sensitive heparansulfate receptor (HSR) of the cells...
2007: Antibiotiki i Khimioterapii︠a︡, Antibiotics and Chemoterapy [sic]
Caroline End, Floris Bikker, Marcus Renner, Gaby Bergmann, Stefan Lyer, Stephanie Blaich, Melanie Hudler, Burkhard Helmke, Nikolaus Gassler, Frank Autschbach, Antoon J M Ligtenberg, Axel Benner, Uffe Holmskov, Peter Schirmacher, Arie V Nieuw Amerongen, Philip Rosenstiel, Christian Sina, Andre Franke, Mathias Hafner, Petra Kioschis, Stefan Schreiber, Annemarie Poustka, Jan Mollenhauer
Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function in mucosal protection and of its broad pathogen-binding specificity. We report that DMBT1 directly interacts with dextran sulfate sodium (DSS) and carrageenan, a structurally similar sulfated polysaccharide, which is used as a texturizer and thickener in human dietary products...
March 2009: European Journal of Immunology
Philipp Sasse, Daniela Malan, Michaela Fleischmann, Wilhelm Roell, Erika Gustafsson, Toktam Bostani, Yun Fan, Thomas Kolbe, Martin Breitbach, Klaus Addicks, Armin Welz, Gottfried Brem, Jürgen Hescheler, Attila Aszodi, Mercedes Costell, Wilhelm Bloch, Bernd K Fleischmann
AIMS: Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, and tissue repair. Loss-of-function mutations in the perlecan gene in mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of the present study was to investigate the mechanism underlying the early embryonic lethality and the pathophysiological relevance of perlecan for heart function...
December 1, 2008: Cardiovascular Research
Dieter Heuss, Janine Klascinski, Steffen W Schubert, Tehmur Moriabadi, Hanns Lochmüller, Said Hashemolhosseini
Motoneurons release the heparansulfate proteoglycan agrin and thereby activate the muscle-specific receptor tyrosine kinase (MuSK), which is the main organizer of subsynaptic specializations at the neuromuscular junction. Recently, we showed that (1) the protein kinase CK2 interacts with the intracellular region of MuSK; (2) the CK2 protein is enriched and co-localized with MuSK at postsynaptic specializations; (3) CK2-mediated phosphorylation of serine residues within a specific MuSK epitope, named the kinase insert, regulates acetylcholine receptor (AChR) clustering; (4) muscle-specific CK2beta knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function (see Genes Dev 20(13):1800-1816, 2006)...
September 2008: Molecular and Cellular Biochemistry
Isabelle Derré, Marc Pypaert, Alice Dautry-Varsat, Hervé Agaisse
Chlamydia spp. are intracellular obligate bacterial pathogens that infect a wide range of host cells. Here, we show that C. caviae enters, replicates, and performs a complete developmental cycle in Drosophila SL2 cells. Using this model system, we have performed a genome-wide RNA interference screen and identified 54 factors that, when depleted, inhibit C. caviae infection. By testing the effect of each candidate's knock down on L. monocytogenes infection, we have identified 31 candidates presumably specific of C...
October 26, 2007: PLoS Pathogens
Shaker Abuharbeid, Frank Czubayko, Achim Aigner
Fibroblast growth factors (FGFs) are important regulators of cell migration, proliferation and differentiation, e.g., during embryogenesis and wound healing, and under several pathological conditions including tumor growth and tumor angiogenesis. Since heparin-binding FGFs are tightly bound to heparansulfate proteoglycans, and therefore, trapped in the extracellular matrix, their release through the action of an FGF-binding protein (FGF-BP) is one of the critical steps in FGF bioactivation. FGF-BP expression is highly tissue specific and strictly regulated through different promoter elements...
2006: International Journal of Biochemistry & Cell Biology
E Ghibaudi, B Boscolo, G Inserra, E Laurenti, S Traversa, L Barbero, R P Ferrari
An ESR investigation of the interaction of spin-labelled penetratin with heparin, heparansulfates and several phospholipid vesicle formulations is reported. Penetratin is a 16-aa peptide corresponding to the third helix of the Antennapedia homeodomain and belonging to the cell-penetrating peptide family. The present study shows that ESR spectroscopy can provide specific and reliable information about the mechanism of interaction of penetratin with polysaccharides and lipids, at a molecular level. The study showed that: (i) heparin and heparansulfates specifically interact with spin-labelled penetratin and promote peptide aggregation and concentration on their molecular surface; (ii) penetratin does not interact with neutral lipids, whereas it enters negatively charged lipid bilayers; (iii) cholesterol plays a negative effect on the insertion of penetratin into the lipid membrane; (iv) the interaction of penetratin with lipid vesicles is strongly dependent on lipid concentration...
July 2005: Journal of Peptide Science: An Official Publication of the European Peptide Society
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