Burr K.L.,University of Dundee |
Robinson J.I.,University of Dundee |
Robinson J.I.,GlycoMar Ltd |
Rastogi S.,University of Dundee |
And 4 more authors.
Radiation Research | Year: 2010
Genetic lesions and cell death associated with exposure to ionizing radiation have generally been attributed to DNA damage arising as a consequence of deposition of energy in the cell nucleus. However, reports of radiation-induced bystander effects, in which DNA damage is produced in nonirradiated cells as a consequence of communication with irradiated cells, indicate additional mechanisms. At present, most information has been obtained using in vitro systems, and the in vivo significance of bystander factors is not clear. In this study we show that signals generated in vivo in the bone marrow of CBA/Ca mice irradiated with 4 Gy γ rays 24 h previously, but not immediately postirradiation, are able to induce DNA damage and apoptosis in nonirradiated bone marrow cells. The signaling mechanism involves FasL, TNF-α, nitric oxide and superoxide and macrophages are implicated as a source of damaging signals. Such delayed bystander-type damage demonstrates the importance of studying tissue responses subsequent to the radiation exposure as well as effects at the time of irradiation when considering the mechanisms underlying the consequences of radiation exposures. © 2010 by Radiation Research Society.
Glycomar Ltd | Date: 2013-05-13
Panagos C.G.,University of Edinburgh |
Panagos C.G.,GlycoMar Ltd |
August D.P.,University of Edinburgh |
Jesson C.,GlycoMar Ltd |
Uhrin D.,University of Edinburgh
Carbohydrate Polymers | Year: 2016
Radical depolymerisation is the method of choice for the depolymerisation of glycosaminoglycans (GAGs), especially when enzymatic depolymerisation cannot be performed due to the lack of suitable enzymes. The established Fenton type free radical depolymerisation generates radicals from a solution of H2O2 in the presence of Cu2+ or Fe2+. When applied to dermatan sulfate (DS), the Fenton type depolymerisation of DS (Panagos, Thomson, Bavington, & Uhrin, 2012) produced exclusively oligosaccharides with reducing end GalNAc, which was partially oxidised to acetylgalactosaminic acid. We report here the results of the TiO2 catalysed photochemical depolymerisation of DS. NMR analysis of these DS oligosaccharides revealed the presence of reducing end IdoA, observed for the first time. The reducing end acetylgalactosaminic acid was also detected. The photochemical depolymerisation method thus enables preparation of new types of GAG oligosaccharides suitable for further biochemical and biological investigation. © 2015 Published by Elsevier Ltd.
Thomson D.,GlycoMar Ltd |
Bavington C.D.,GlycoMar Ltd
Carbohydrate Polymers | Year: 2012
The contamination of heparin in 2008 brought to the attention of health authorities an urgent need for structural characterisation of low molecular weight heparins and other glycosaminoglycans (GAGs) intended for clinical applications. Potentially harmful compounds can be introduced into these preparations as contaminants of the original material or as by-products of the depolymerisation process. Radical depolymerisation is one of the methods used for fractionations of GAGs. We report here on the results of the Fenton-type radical depolymerisation of dermatan sulfate (DS) by hydrogen peroxide in the presence of Cu 2+ cations. A low molecular fraction of the reaction mixture was investigated by a combination of 2D 1H, 13C HSQC, 2D HSQC-TOCSY and 2D HMBC experiments at 800 MHz. The analysis of the spectra revealed the formation of oligosaccharides with structures corresponding to the native DS sequence and containing almost exclusively GalNAc4S as the reducing end monosaccharide. In addition, oligosaccharides containing a C-4 sulfated N-acetylgalactosaminic acid in place of the reducing end GalNAc4S were identified. This open chain monosaccharide represents a non-native DS structure. © 2011 Elsevier Ltd. All rights reserved.
Thomson D.,GlycoMar Ltd |
Venkatasamy R.,Kings College London |
Moss C.,GlycoMar Ltd |
Robinson J.,GlycoMar Ltd |
And 6 more authors.
Pulmonary Pharmacology and Therapeutics | Year: 2016
It is now recognized that certain polysaccharides can exhibit anti-inflammatory activity, including the glycosaminoglycan (GAG) heparin that is widely used as an anti-coagulant drug. However, it would be desirable to identify molecules that retain the anti-inflammatory actions of heparin, but that are devoid of significant anti-coagulant activity. In the present study we have identified a number of novel GAG and GAG-like polysaccharides (VRP327) from marine organisms, most of which were resistant to digestion by heparinase II and chondroitinase ABC. Fourier transform infra-red spectrum (FTIR) revealed species with variable degrees of sulphation and monosaccharide analysis revealed a range of sugar compounds, which in some cases included sugars not present in mammalian GAGs. 1H NMR spectra of these species are consistent with the structures of complex polysaccharides. From an initial screening cascade to remove compounds having significant anti-coagulant activity and no overt cytotoxicity, we identified a high molecular weight oversulphated dermatan sulphate (VRP327) isolated from the tunicate Ascidiella aspersa which was fully characterised by NMR spectroscopy. This material was depolymerised to produce well characterized low molecular weight fractions which were demonstrated to be non-toxic, with low levels of anti-coagulant activity, and to have demonstrable anti-inflammatory activity assessed in several in vitro and in vivo models. The identification of low molecular weight polysaccharides having significant anti-inflammatory activity without significant anti-coagulant activity may provide novel templates for the development of a novel class of anti-inflammatory drugs. © 2016 Elsevier Ltd