Navegando por Palavras-chave "Chondroitin sulfate"
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- ItemSomente Metadadados2,3-Di-O-sulfo glucuronic acid: An unmodified and unusual residue in a highly sulfated chondroitin sulfate from Litopenaeus vannamei(Elsevier Sci Ltd, 2018) Cavalcante, Romulo S.; Brito, Adriana S.; Palhares, Lais C. G. F.; Lima, Marcelo A. [UNIFESP]; Cavalheiro, Renan P. [UNIFESP]; Nader, Helena B. [UNIFESP]; Sassaki, Guilherme L.; Chavante, Suely F.The occurrence of a natural and unmodified highly sulfated chondroitin sulfate from Litopenaeus vannamei heads (sCS) is herein reported. Its partial digestion by Chondroitinases AC and ABC together with its electrophoretic migration profile revealed it as a highly sulfated chondroitin sulfate despite its average molecular weight being similar to CSA. Using orthogonal 1D/2D NMR experiments, the anomeric signals (delta 4.62/106.0) corresponding to unusual 2,3-di-O-Sulfo-GlcA (similar to 36%), U3(3S) (delta 4.42/84.1, similar to 63%) and U2(2S) (4.12/80.1, similar to 50%) substitutions were confirmed. In addition, non-sulfated GlcA (delta 4.5/106.3) linked to 4-O-(A1(4S), 36%) or 6-O-Sulfo (A1(6S), 28%) GalNAc (delta 4.64/103.5) was observed. Although the biological role of sCS in shrimp is unknown, its influence on hemostasis was also demonstrated. The sCS identification brings to light new questions about the hierarchical model of GAGs biosynthesis and contributes to the better understanding of the subtle relationship between GAGs structure and function.
- ItemSomente MetadadadosChondroitin sulfate and glucosamine sulfate associated to photobiomodulation prevents degenerative morphological changes in an experimental model of osteoarthritis in rats(Springer London Ltd, 2018) Sanches, Marcella [UNIFESP]; Assis, Livia [UNIFESP]; Criniti, Cyntia [UNIFESP]; Fernandes, Danilo [UNIFESP]; Tim, Carla [UNIFESP]; Renno, Ana Claudia Muniz [UNIFESP]The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG)
- ItemAcesso aberto (Open Access)Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation(Humana Press Inc, 2018) Galindo, Layla Testa [UNIFESP]; Mundim, Mayara T. V. V. [UNIFESP]; Pinto, Agnes S. [UNIFESP]; Chiarantin, Gabrielly Maria Denadai [UNIFESP]; Almeida, Maira E. S.; Lamers, Marcelo L.; Horwitz, Alan R.; Santos, Marinilce F.; Porcionatto, Marimélia Aparecida [UNIFESP]Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
- ItemSomente MetadadadosChondroitin sulfate interacts mainly with headgroups in phospholipid monolayers(Elsevier Science Bv, 2016) Ceridorio, Lucineia F. [UNIFESP]; Caseli, Luciano [UNIFESP]; Oliveira, Osvaldo N., Jr.Sulfated glycosaminoglycans are precursors of the extracellular matrix used to treat diseases related to blood clotting and degenerative joint diseases. These medical applications have been well established, but the mode of action at the molecular level, which depends on the interaction with cell membranes, is not known in detail. In this study, we investigated the interaction between chondroitin sulfate (CS) and phospholipid monolayers that mimic cell membranes. From surface pressure isotherms and polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS), CS was found to interact mainly with the polar groups of dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl phosphatidylglycerol (DPPG), with negligible penetration into the hydrophobic tails and only small changes in monolayer elasticity for the packing corresponding to a real cell membrane. The changes in surface pressure and surface potential isotherms depended on CS concentration and on the time allowed for its adsorption onto the monolayer, which points to a dynamic adsorption-desorption process. The charge of the phospholipid was also relevant, since CS induced order into DPPC monolayers while the opposite occurred for DPPG, according to the PM-IRRAS spectra. In summary, interaction with polar groups is responsible for the CS effects on model cell membranes. (C) 2016 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosDo chondroitin sulfates with different structures have different activities on chondrocytes and macrophages?(Elsevier Science Bv, 2017) da Cunha, Andre L. [UNIFESP]; Aguiar, Jair A. K. [UNIFESP]; Correa da Silva, Flavio S.; Michelacci, Yara M. [UNIFESP]The aim of the present study was to investigate the activities of natural chondroitin sulfates (CS) with different structures on cultured chondrocytes and macrophages. CS were isolated from cartilages of bovine trachea (BT), porcine trachea (PT), chicken sternum (Ch) and skate (Sk). The preparations were 90-98% pure, with similar to 1% proteins, nucleic acids and keratan sulfate contaminants. Structural analysis of these CS and of commercial chondroitin 4- and 6-sulfate (C4S, C6S) have shown that most of their disaccharides are monosulfated, with varying proportions of 4- and 6-sulfation, and 2-7% non-sulfated disaccharides. Sk-CS and C6S contained detectable amounts of disulfated disaccharides. All the CS were polydisperse, with modal molecular weights of 26-135 kDa. These CS had anti-inflammatory activities on both chondrocytes and macrophages, but with different efficiencies. On horse and human chondrocytes, they reduced the IL-1 beta-induced liberation of NO and PGE(2), and on RAW 264.7 immortalized macrophage-like cell line, C4S, C6S, Ch and Sk-CS decreased the LPS-induced liberation of TNF-alpha, but did not affect IL-6. In contrast, on bone marrow derived macrophages, C4S, C6S, BT and PT-CS reduced the LPS-induced liberation of TNF-alpha, IL-6, IL-1 beta and NO, indicating that the RAW response to CS was different from that of primary macrophages. (C) 2017 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Efeito do condroitim sulfato na fibrogênese hepática induzida por ligadura do ducto biliar em ratos(Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Guedes, Pedro Luiz Rodrigues [UNIFESP]; Nagaoka, Márcia Regina [UNIFESP]; http://lattes.cnpq.br/3554142919645884; http://lattes.cnpq.br/4997715000909196; Universidade Federal de São Paulo (UNIFESP)Introdução: Uma das causas de fibrose hepática é a colestase, que causa morte celular e desencadeia a liberação de citocinas e quimiocinas, levando à infiltração de leucócitos e à deposição de matriz extracelular. O tratamento atual da fibrose hepática é baseado na retirada do agente causador, por isso é importante a investigação de estratégias novas e eficazes para o tratamento da fibrose hepática. Muitos estudos destacam a ação do condroitim sulfato em diferentes tipos de células, com consequente redução da expressão de citocinas. O objetivo deste trabalho foi analisar os efeitos do condroitim sulfato (CS) sobre o modelo experimental de colestase extra-hepática induzida pela ligadura do ducto biliar comum (BDL). Metodologia: Ratos Wistar (6-8 semanas) foram submetidos a BDL e receberão injeção intraperitoneal de CS (120 mg/kg peso) ou veículo por 1, 2, 7, 14, 21 ou 28 dias; os animais sham foram utilizados como controle. Ao final do período de tratamento, os animais foram eutanasiados e amostras de fígado e sangue retiradas. Foram analisadas as atividades de alanina e aspartato aminotransferases séricas (ALT e AST, respectivamente) e, caspase-3 e catepsina B em homogenatos de fígado utilizando os substratos fluorométricos Ac-DEVD-AMC e Abz-GIVRAK(Dnp)-OH, respectivamente. Em espécimes de fígado foi realizada análise morfométrica usando o programa Axiovision 4,8, além de avaliar a apoptose por reação de TUNEL e regeneração hepática por imuno-histoquímica para o antígeno nuclear de proliferação celular (PCNA).. Os resultados foram expressos pela média ± EPM. A análise estatística de valores padronizados foi realizada por ANOVA unidirecional com post-hoc de Tukey. Resultados: Animais BDL apresentaram atividades séricas de ALT e AST 2-3 vezes maiores do que os sham. BDL levou ao progressivo desenvolvimento de septos fibróticos, confirmado pela área de colágeno (%) após 7 (11 ± 1, n = 7), 14 (14 ± 1, n = 10), 21 (23 ± 1, n = 4) e 28 (34 ± 3, n = 7) dias de indução, enquanto os grupos sham tiveram a arquitetura normal do fígado preservada. O tratamento com CS reduziu o conteúdo de colágeno após 21 dias (14 ± 1, n = 6) e significativamente (p <0,001) após 28 dias (16 ± 2, n = 6) em relação ao não-tratado. Não foram observadas alterações significativas nas atividades da catepsina B de todos os grupos estudados. Verificou-se aumento progressivo da atividade da caspase-3 (relativo ao sham) no grupo BDL 2d (1,4 ± 0,1, n = 5), BDL 7d (2,2 ± 0,6, n = 7) e 14d (3,3 ± 0,5, n = 10; ANOVA, p < 0,001) quando comparados aos respectivos grupos sham. Interessante, CS reduziu significativamente (p= 0,024) a atividade de caspase-3 após 14 dias de tratamento (1,7 ±0,7, n = 9) quando comparado com o grupo BDL 14d. Os animais BDL apresentaram mais células apoptóticas por campo (% do total) aos 14 dias (0,58±0,04) do que aos 7 (0,25±0,02), 21 (0,33±0,02) e 28 dias (0,29±0,01). O tratamento com CS reduziu significativamente (p = 0,030) a quantidade de células em apoptose nos animais 14d (0,43±0,04). BDL levou ao aumento significativo na quantidade relativa (%) de células epiteliais biliares e de hepatócitos com núcleo marcado com anti-PCNA. O tratamento com CS levou ao aumento significativo de hepatócitos em proliferação (No relativo) nos animais 14d (2,9±0,1 – ANOVA; p = 0,003) e 21d (3,5±0,2 - ANOVA; p < 0,001) quando comparados aos respectivos BDL não tratados (14d: 2,1±0,1 e 21d: 2,2±0,21). Conclusão: Este trabalho mostra que a CS pode reduzir os primeiros sinais de apoptose, retardar o desenvolvimento de fibrose hepática e, portanto, cirrose, além de promover a regeneração hepática em modelo experimental de ligadura do ducto biliar.
- ItemAcesso aberto (Open Access)Extracellular matrix alterations in the Peyronie's disease(Elsevier Science Bv, 2017) Watanabe, Marcelo Silva; Theodoro, Therese Rachel; Coelho, Natalia Lima [UNIFESP]; Mendes, Aline [UNIFESP]; Pereira Leonel, Monica Luzia; Mader, Ana Maria; Nader, Helena Bonciani [UNIFESP]; Glina, Sidney; Silva Pinhal, Maria Aparecida [UNIFESP]Peyronie's disease is characterized by fibrous plaque formation of the tunica albuginea, causing penile deformity and fertility problems. The aim of the present study was to investigate alterations in the extracellular matrix in Peyronie's disease. The study used tissues collected by surgical procedure from individuals that presented a well-established disease, while control samples were obtained by biopsies of fresh cadavers. Immunohistochemistry analysis followed by digital quantification was performed to evaluate TGF-beta, heparanases and metalloproteinases (MMPs). The profile of sulfated glycosaminoglycans, chondroitin sulfate and dermatan sulfate was determined by agarose gel electrophoresis, while hyaluronic acid quantification was obtained by an ELISA-like assay. The expression of mRNA was investigated for syndecan-1 proteoglycan (Syn-1), interleukine-6 (IL-6), hyaluronic acid synthases, and hyaluronidases. Pathologic features showed decreased apoptosis and blood vessel number in Peyronie's tissues. TGF-beta and IL-6 were significantly enhanced in Peyronie's disease. There was an increased expression of heparanases, though no alteration was observed for MMPs. Hyaluronic acid as well as hyaluronic acid synthases, hyaluronidases, and dermatan sulfate were not changed, while the level of chondroitin sulfate was significantly (P = 0.008, Mann-Whitney test) increased in Peyronie's samples. Heparanases and sulfated glycosaminoglycans seem to be involved in extracellular matrix alterations in Peyronie's disease. (C) 2017 Production and hosting by Elsevier B.V. on behalf of Cairo University.
- ItemAcesso aberto (Open Access)Gradual strenuous running regimen predisposes to osteoarthritis due to cartilage cell death and altered levels of glycosaminoglycans(Elsevier B.V., 2013-07-01) Franciozi, Carlos Eduardo da Silveira [UNIFESP]; Tarini, Victor Alexandre Ferreira [UNIFESP]; Reginato, Rejane Daniele [UNIFESP]; Gonçalves, Patrícia dos Reis Sousa [UNIFESP]; Medeiros, Valquíria Pereira de [UNIFESP]; Ferretti, Mario [UNIFESP]; Dreyfuss, Juliana Luporini [UNIFESP]; Nader, Helena Bonciani [UNIFESP]; Faloppa, Flávio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To investigate the hypothesis that strenuous running is a predisposing factor for osteoarthritis.Design: Wistar rats were divided into two groups: a control group (CG) and a trained group (TG). the TG underwent a strenuous treadmill running training regimen of controlled intensity, exhibiting progressively improvement of fitness over 12 weeks, running at least 55 km during this period and finally performing an ultra-endurance running exercise to exhaustion. After this period, rats from both groups were euthanized and their knees removed. the articular cartilage was dissected and submitted to histomorphometrical, histomorphological, and immunohistochemical analyses evaluating cell death pathway (caspase-3 and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick 'end labeling (TUNEL)) and inflammatory cytokines [interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha)]. in addition, the tissues were analyzed regarding the types and the content of glycosaminoglycans.Results: the TG knee joints exhibited increase in the number of chondrocytes and chondrocyte clusters, as well as significantly increased levels of caspase-3, a protein involved in apoptosis, and of inflammatory cytokines IL-1 alpha and TNF-alpha. in addition, histologically higher grades of osteoarthritis (Osteoarthritis Research Society International - OARSI grading), and significantly decreased levels of chondroitin sulfate and hyaluronic acid. Knee cartilage thickness and TUNEL did not significantly differ between the two groups.Conclusions: the articular cartilage of rats subjected to a strenuous running regimen of controlled intensity exhibited molecular and histological characteristics that are present in osteoarthritis. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosUrinary glycosaminoglycans in horse osteoarthritis. Effects of chondroitin sulfate and glucosamine(Elsevier B.V., 2012-08-01) Baccarin, Raquel Yvonne Arantes; Machado, Thais S. L.; Lopes-Moraes, Ana P.; Vieira, Fabiana A. C. [UNIFESP]; Michelacci, Yara M. [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Our objectives were to characterize the urinary excretion of glycosaminoglycans (GAGs) in horse osteoarthritis, and to investigate the effects of chondroitin sulfate (CS) and glucosamine (GlcN) upon the disease. Urinary GAGs were measured in 47 athletic horses, 20 healthy and 27 with osteoarthritis. the effects of CS and GlcN were investigated in mild osteoarthritis. in comparison to normal, urinary GAGs were increased in osteoarthritis, including mild osteoarthritis affecting only one joint. Treatment with CS + GlcN led to a long lasting increase in the urinary CS and keratan sulfate (KS), and significant improvement in flexion test of tarsocrural and metacarpophalangeal joints was observed. in conclusion, urinary CS and KS seems to reflect the turnover rates of cartilage matrix proteoglycans, and the measurement of these compounds could provide objective means of evaluating and monitoring joint diseases. (C) 2011 Elsevier B.V. All rights reserved.