Home About us Contact
|
Home About us Contact | ||
|
|
||
Heparan Sulphate (heparan + sulphate)
Terms modified by Heparan Sulphate Selected AbstractsDevelopmental changes in cellular and extracellular structural macromolecules in the secondary palate and in the nasal cavity of the mouseEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2010Forugh Vaziri Sani Vaziri Sani F, Kaartinen V, El Shahawy M, Linde A, Gritli-Linde A. Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and nasal cavity of the mouse. Eur J Oral Sci 2010; 118: 221,236. © 2010 The Authors. Journal compilation© 2010 Eur J Oral Sci The aim of this study was to analyse the hitherto largely unknown expression patterns of some specific cellular and extracellular molecules during palate and nasal cavity development. We showed that epithelia of the developing palate and the vomerine epithelium express similar sets of structural proteins. With the exception of keratin 15, which becomes barely detectable in the elevated palatal shelves, nearly all of these proteins become upregulated at the presumptive areas of fusion and in the adhering epithelia of the palate and nasal septum. In vivo and in vitro analyses indicated that reduction in the amount of keratin 15 protein is independent of Tgf,,Alk5 signalling. Foxa1 expression also highlighted the regionalization of the palatal and nasal epithelia. Owing to the lack of reliable markers of the palatal periderm, the fate of peridermal cells has been controversial. We identified LewisX/stage-specific embryonic antigen-1 as a specific peridermal marker, and showed that numerous peridermal cells remain trapped in the medial epithelial seam (MES). The fate of these cells is probably apoptosis together with the rest of the MES cells, as we provided strong evidence for this event. Heparan sulphate, chondroitin-6-sulphate, and versican displayed dynamically changing distribution patterns. The hitherto-unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting. [source] Examination of intravenous and intra-CSF protein delivery for treatment of neurological diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Kim M. Hemsley Abstract Mucopolysaccharidosis type IIIA is a neurodegenerative lysosomal storage disorder characterized by progressive loss of learned skills, sleep disturbance and behavioural problems. Absent or greatly reduced activity of sulphamidase, a lysosomal protein, results in intracellular accumulation of heparan sulphate. Subsequent neuroinflammation and neurodegeneration typify this and many other lysosomal storage disorders. We propose that intra-cerebrospinal fluid protein delivery represents a potential therapeutic avenue for treatment of this and other neurodegenerative conditions; however, technical restraints restrict examination of its use prior to adulthood in mice. We have used a naturally-occurring Mucopolysaccharidosis type IIIA mouse model to determine the effectiveness of combining intravenous protein replacement (1 mg/kg) from birth to 6 weeks of age with intra-cerebrospinal fluid sulphamidase delivery (100 ,g, fortnightly from 6 weeks) on behaviour, the level of heparan sulphate-oligosaccharide storage and other neuropathology. Mice receiving combination treatment exhibited similar clinical improvement and reduction in heparan sulphate storage to those only receiving intra-cerebrospinal fluid enzyme. Reductions in micro- and astrogliosis and delayed development of ubiquitin-positive lesions were seen in both groups. A third group of intravenous-only treated mice did not exhibit clinical or neuropathological improvements. Intra-cerebrospinal fluid injection of sulphamidase effectively, but dose-dependently, treats neurological pathology in Mucopolysaccharidosis type IIIA, even when treatment begins in mice with established disease. [source] Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations,HUMAN MUTATION, Issue 5 2010Marlies J. Valstar Abstract Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 in-frame small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene. © 2010 Wiley-Liss, Inc. [source] A Hibiscus Abelmoschus seed extract as a protective active ingredient to favour FGF-2 activity in skinINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2009D. Rival Synopsis In the skin, heparin, heparan sulphate and heparan sulphate proteoglycans control the storage and release of growth factors and protect them from early degradation. We developed a cosmetic active ingredient containing Hibiscus Abelmoschus seed extract (trade name LinefactorÔ) that can maintain the FGF-2 content in the skin by mimicking the protective effect of heparan sulphate proteoglycans. By preventing the natural degradation of FGF-2, Hibiscus Abelmoschus seed extract maintains the bioavailability of this growth factor for its target cells, i.e. skin fibroblasts. Our in vitro evaluations showed that this ingredient exhibited heparan sulphate-like properties and dose-dependently protected FGF-2 from thermal degradation. We could also show that, in turn, the protected FGF-2 could stimulate the synthesis of sulphated GAGs, the natural protective molecules for FGF-2, thus providing a double protection. Finally, the in vitro results were confirmed in vivo thanks to a clinical study in which skin biomechanical properties and reduction in wrinkles were assessed. Résumé Dans la peau, l'héparane sulfate et les protéoglycanes à héparane sulfate contrôlent le stockage et la libération des facteurs de croissance et les protègent de la dégradation prématurée. Nous avons développé un actif cosmétique contenant un extrait de graines d'Hibiscus Abelmoschus capable de maintenir le contenu en FGF-2 de la peau en mimant l'effet protecteur des protéoglycanes à héparane sulfate. En prévenant la dégradation naturelle du FGF-2, l'extrait de graines d'Hibiscus Abelmoschus maintient la biodisponibilité de ce facteur de croissance pour ses cellules cibles que sont les fibroblastes de la peau. Les évaluations in vitro ont montré que cet ingrédient possédait des propriétés « héparane sulfate-like » et protégeait le FGF-2 de la dégradation thermique de façon dose-dépendante. Nous avons également pu montrer qu'en retour, le FGF-2 protégé pouvait stimuler la synthèse de GAGs sulfatés naturellement protecteurs du FGF-2, offrant ainsi une double protection. Enfin, les résultats in vitro ont été confirmés in vivo par une étude clinique au cours de laquelle les propriétés biomécaniques de la peau ainsi que la réduction des rides ont étéévaluées. [source] GAG Mimetic Libraries: Sulphated Peptide as Heparin-like Glycosaminoglycan Mimics in Their Interaction with FGF-1MOLECULAR INFORMATICS, Issue 8 2005Socorro Vázquez-Campos Abstract Heparin and heparan sulphate (HS) are heterogenous, linear, polysulphated polysaccharides that are important in the regulation of a wide variety of biological processes including blood coagulation, in cell differentiation, adhesion, invasion, migration and development, and in tumor-related cellular events such as growth regulation and metastasis. In general, heparin/HS interacts with proteins mainly through ionic interactions between its negatively charged groups and positively charged groups on the proteins. From a mechanistic or therapeutic standpoint, it is attractive to design less complex charged molecules, other than oligosaccharides, as mimics of heparin. In an attempt to improve the accessibility of heparin mimics, it was assumed, provided that the correct charge topography could be achieved, that sulphated peptides might also act as mimics. Therefore, sulphated peptide combinatorial libraries were generated on solid support to identify novel polyanionic structures that mimic the role of heparin/HS in its binding to fibroblast growth factors (FGFs). Libraries were synthesised by direct sulphation of the peptide on solid phase or by using O- sulphonated building blocks during peptide synthesis. Quantitative solid-phase O -sulphonation of hydroxy amino acid residues in a peptide chain was effected by sulphur trioxide pyridine (SO3 -Pyr) complex in anhydrous pyridine at 65,°C for 4,h. O- Sulphonated building blocks were successfully synthesised in solution and, after stabilisation of the sulphate group by complexion with tetrabutyl ammonium ions, were employed in the synthesis of sulphated peptide libraries, similar to those generated by direct O- sulphonation on solid supports. The libraries were incubated with fluorescent-labelled FGF-1, and analysis and sequence determination of active compounds was carried out using Edman degradation. Selected sulphated peptides from the screening were resynthesised and their affinity for FGF-1 (acidic FGF) was studied in solution competition assays using surface plasmon resonance. These studies showed that sulphated decapeptides do bind to FGF-1 and inhibit its binding to immobilised heparin in the low micromolar concentration range. [source] Correction of mucopolysaccharidosis type IIIA somatic and central nervous system pathology by lentiviral-mediated gene transferTHE JOURNAL OF GENE MEDICINE, Issue 9 2010Chantelle McIntyre Abstract Background The hallmark of lysosomal storage disorders (LSDs) is microscopically demonstrable lysosomal distension. In mucopolysaccharidosis type IIIA (MPS IIIA), this occurs as a result of an inherited deficiency of the lysosomal hydrolase sulphamidase. Consequently, heparan sulphate, a highly sulphated glycosaminoglycan, accumulates primarily within the cells of the reticulo-endothelial and monocyte-macrophage systems and, most importantly, neurones. Children affected by MPS IIIA experience a severe, progressive neuropathology that ultimately leads to death at around 15 years of age. Methods MPS IIIA pathology was addressed in a mouse model using two separate methods of therapeutic gene delivery. A lentiviral vector expressing murine sulphamidase was delivered to 6-week-old MPS IIIA affected mice either by intravenous injection, or by intraventricular infusion. Therapeutic outcomes were assessed 7 months after gene transfer. Results After intravenous gene delivery, liver sulphamidase was restored to approximately 30% of wild-type levels. The resultant widespread delivery of enzyme secreted from transduced cells to somatic tissues via the peripheral circulation corrected most somatic pathology. However, unlike an earlier study, central nervous system (CNS) pathology remained unchanged. Conversely, intraventricular gene delivery resulted in widespread sulphamidase gene delivery in (and reduced lysosomal storage throughout) the brain. Improvements in behaviour were observed in these mice, and interestingly, pathological urinary retention was prevented. Conclusions The CNS remains the last major barrier to effective therapy for children affected by LSDs. The blood,brain barrier (BBB) limits the uptake of lysosomal enzymes from the peripheral circulation into the CNS, making direct gene delivery to the brain a reasonable, albeit more challenging, therapeutic option. Future work will further assess the relative advantages of directly targeting the brain with somatic gene delivery with sulphamidase modified to increase the efficiency of transport across the BBB. Copyright © 2010 John Wiley & Sons, Ltd. [source] Heparanase expression during normal liver development and following partial hepatectomyTHE JOURNAL OF PATHOLOGY, Issue 1 2004Orit Goldshmidt Abstract Heparan sulphate proteoglycans are major components of the liver extracellular matrix. Their cleavage by heparanase (endo-,-glucuronidase) may thus be involved in liver-specific normal and pathological processes. Heparanase mRNA and protein were expressed during liver development but not in the mature healthy liver. A biphasic gain of heparanase expression, detected by immunostaining, western blotting, and real-time RT-PCR, was clearly noted following partial hepatectomy, peaking at 12 and 96,168 h and subsiding 2 weeks post-surgery. Expression of heparan sulphate gradually increased throughout the regeneration process. Unlike heparanase, baseline levels of matrix metalloproteinase-2 (MMP-2) were detected in the intact liver, increasing up to 4 days following partial hepatectomy and subsiding at day 10. Bands matching MMP-9 were absent prior to hepatectomy, but visible 2 h post-hepatectomy. Thioacetamide-induced liver fibrosis was associated with increased levels of MMP-9 and MMP-2, correlating with the severity of the disease. Elevated heparanase levels were noted in the early stages of fibrosis, with no further increase evident in rats exhibiting higher fibrotic grades. Taken together, these data suggest a role for heparanase during liver development and remodelling. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||