18 research outputs found
Urochordate Histoincompatible Interactions Activate Vertebrate-Like Coagulation System Components
The colonial ascidian Botryllus schlosseri expresses a unique allorecognition system. When two histoincompatible Botryllus colonies come into direct contact, they develop an inflammatory-like rejection response. A surprising high number of vertebrates' coagulation genes and coagulation-related domains were disclosed in a cDNA library of differentially expressed sequence tags (ESTs), prepared for this allorejection process. Serine proteases, especially from the trypsin family, were highly represented among Botryllus library ortholgues and its âmolecular functionâ gene ontology analysis. These, together with the built-up clot-like lesions in the interaction area, led us to further test whether a vertebrate-like clotting system participates in Botryllus innate immunity. Three morphologically distinct clot types (points of rejection; POR) were followed. We demonstrated the specific expression of nine coagulation orthologue transcripts in Botryllus rejection processes and effects of the anti-coagulant heparin on POR formation and heartbeats. In situ hybridization of fibrinogen and von Willebrand factor orthologues elucidated enhanced expression patterns specific to histoincompatible reactions as well as common expressions not augmented by innate immunity. Immunohistochemistry for fibrinogen revealed, in naĂŻve and immune challenged colonies alike, specific antibody binding to a small population of Botryllus compartment cells. Altogether, molecular, physiological and morphological outcomes suggest the involvement of vertebrates-like coagulation elements in urochordate immunity, not assigned with vasculature injury
Dermatan sulfate reduces monocyte chemoattractant protein 1 and TGF-ÎČ production, as well as macrophage recruitment and myofibroblast accumulation in mice with unilateral ureteral obstruction
Prevalence of depression morbidity among Brazilian adults: a systematic review and meta-analysis
Interactions of hepatocyte growth factor / scatter factor with various glycosaminoglycans reveal an important interplay between the presence of iduronate and sulfate density.
Hepatocyte growth factor/scatter factor (HGF/SF) has a cofactor requirement for heparan sulfate (HS) and dermatan sulfate (DS) in the optimal activation of its signaling receptor MET. However, these two glycosaminoglycans (GAGs) have different sugar backbones and sulfation patterns, with only the presence of iduronate in common. The structural basis for GAG recognition and activation is thus very unclear. We have clarified this by testing a wide array of natural and modified GAGs for both protein binding and activation. Comparisons between Ascidia nigra (2,6-O-sulfated) and mammalian (mainly 4-O-sulfated) DS species, as well as between a panel of specifically desulfated heparins, revealed that no specific sulfate isomer, in either GAG, is vital for interaction and activity. Moreover, different GAGs of similar sulfate density had comparable properties, although affinity and potency notably increase with increasing sulfate density. The weaker interaction with CS-E, compared with DS, shows that GlcA-containing polymers can bind, if highly sulfated, but emphasizes the importance of the flexible IdoA ring. Our data indicate that the preferred binding sites in DS in vivo will be comprised of disulfated, IdoA(2S)-containing motifs. In HS, clustering of N-/2-O-/6-O-sulfation in S-domains will lead to strong reactivity, although binding can also be mediated by the transition zones where sulfates are mainly at the N- and 6-O- positions. GAG recognition of HGF/SF thus appears to be primarily driven by electrostatic interactions and exhibits an interesting interplay between requirements for iduronate and sulfate density that may reflect in part a preference for particular sugar chain conformations
Design and optimization of energy-efficient single mixed refrigerant LNG liquefaction process
Composition of Glycosaminoglycans in Elasmobranchs including Several Deep-Sea Sharks: Identification of Chondroitin/Dermatan Sulfate from the Dried Fins of Isurus oxyrinchus and Prionace glauca
The specificity of interactions between proteins and sulfated polysaccharides
Sulfated polysaccharides are capable of binding with proteins at several levels of specificity. As highly acidic macromolecules, they can bind non-specifically to any basic patch on a protein surface at low ionic strength, and such interactions are not likely to be physiologically significant. On the other hand, several systems have been identified in which very specific substructures of sulfated polysaccharides confer high affinity for particular proteins; the best-known example of this is the pentasaccharide in heparin with high affinity for antithrombin, but other examples may be taken from the study of marine invertebrates: the importance of the fine structure of dermatan sulfate (DS) to its interaction with heparin cofactor II (HCII), and the involvement of sea urchin egg-jelly fucans in species specific fertilization. A third, intermediate, kind of specific interaction is described for the cell-surface glycosaminoglycan heparan sulfate (HS), in which patterns of sulfate substitution can show differential affinities for cytokines, growth factors, and morphogens at cell surfaces and in the intracellular matrix. This complex interplay of proteins and glycans is capable of influencing the diffusion of such proteins through tissue, as well as modulating cellular responses to them.<br>Os polissacarĂdeos sulfatados sĂŁo capazes de se ligar Ă s proteĂnas com diferentes nĂveis de especificidade. SĂŁo macromolĂ©culas altamente ĂĄcidas que podem se ligar de forma inespecĂfica a qualquer domĂnio bĂĄsico da superfĂcie de uma proteĂna em soluçÔes com baixa força iĂŽnica, contudo tais interaçÔes nĂŁo parecem ser fisiologicamente significativas. Por outro lado, foram identificados vĂĄrios sistemas nos quais componentes estruturais muito especĂficos dos polissacarĂdeos sulfatados conferem alta afinidade para algumas proteĂnas. O exemplo mais conhecido Ă© o pentassacarĂdeo da heparina com alta afinidade pela antitrombina. Outros exemplos podem ser observados no estudo de invertebrados marinhos, tais como a importĂąncia da estrutura fina do dermatam sulfato para sua interação com o cofator II da heparina e o envolvimento defucanas sulfatadas encontradas no gel que envolve osĂłvulos dos ouriços-do-mar na espĂ©cie especificidade da fertilização. Um terceiro exemplo de interação especĂfica Ă© aquele descrito para o glicosaminoglicano heparam sulfato encontrado na superfĂcie celular. Neste caso, o padrĂŁo de sulfatação pode determinar diferentes afinidades do carboidrato por citoquinas, fatores de crescimento e outras proteĂnas encontradas na superfĂcie celular e na matriz extracelular. Estas interaçÔes complexas entre proteĂnas e carboidratos sĂŁo capazes de influenciar a difusĂŁo das proteĂnas atravĂ©s dos tecidos, assim como modelar a resposta celular a estas molĂ©culas